Author: "Northcott, Paul A" / Database: OAIster - Searchworks@Jio Institute Digital Library Search Results

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85 results on '"Northcott, Paul A"'

1. PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression

Author: Schmidt, Christin, Schmidt, Christin, Cohen, Sarah, Gudenas, Brian L, Husain, Sarah, Carlson, Annika, Westelman, Samantha, Wang, Linyu, Phillips, Joanna J, Northcott, Paul A, Weiss, William A, Schwer, Bjoern, Schmidt, Christin, Schmidt, Christin, Cohen, Sarah, Gudenas, Brian L, Husain, Sarah, Carlson, Annika, Westelman, Samantha, Wang, Linyu, Phillips, Joanna J, Northcott, Paul A, Weiss, William A, and Schwer, Bjoern
Abstract: SNCAIP duplication may promote Group 4 medulloblastoma via induction of PRDM6, a poorly characterized member of the PRDF1 and RIZ1 homology domain-containing (PRDM) family of transcription factors. Here, we investigated the function of PRDM6 in human hindbrain neuroepithelial stem cells and tested PRDM6 as a driver of Group 4 medulloblastoma. We report that human PRDM6 localizes predominantly to the nucleus, where it causes widespread repression of chromatin accessibility and complex alterations of gene expression patterns. Genome-wide mapping of PRDM6 binding reveals that PRDM6 binds to chromatin regions marked by histone H3 lysine 27 trimethylation that are located within, or proximal to, genes. Moreover, we show that PRDM6 expression in neuroepithelial stem cells promotes medulloblastoma. Surprisingly, medulloblastomas derived from PRDM6-expressing neuroepithelial stem cells match human Group 3, but not Group 4, medulloblastoma. We conclude that PRDM6 expression has oncogenic potential but is insufficient to drive Group 4 medulloblastoma from neuroepithelial stem cells. We propose that both PRDM6 and additional factors, such as specific cell-of-origin features, are required for Group 4 medulloblastoma. Given the lack of PRDM6 expression in normal tissues and its oncogenic potential shown here, we suggest that PRDM6 inhibition may have therapeutic value in PRDM6-expressing medulloblastomas.
Published: 2024

2. The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors

Author: Bartl, Jasmin, Zanini, Marco, Bernardi, Flavia, Forget, Antoine, Blümel, Lena, Talbot, Julie, Picard, Daniel, Qin, Nan, Cancila, Gabriele, Gao, Qingsong, Nath, Soumav, Koumba, Idriss Mahoungou, Wolter, Marietta, Kuonen, François, Langini, Maike, Beez, Thomas, Munoz, Christopher, Pauck, David, Marquardt, Viktoria, Yu, Hua, Souphron, Judith, Korsch, Mascha, Mölders, Christina, Berger, Daniel, Göbbels, Sarah, Meyer, Frauke-Dorothee, Scheffler, Björn, Rotblat, Barak, Diederichs, Sven, Ramaswamy, Vijay, Suzuki, Hiromishi, Oro, Anthony, Stühler, Kai, Stefanski, Anja, Fischer, Ute, Leprivier, Gabriel, Willbold, Dieter, Steger, Gerhard, Buell, Alexander, Kool, Marcel, Lichter, Peter, Pfister, Stefan M., Northcott, Paul A., Taylor, Michael D., Borkhardt, Arndt, Reifenberger, Guido, Ayrault, Olivier, Remke, Marc, Bartl, Jasmin, Zanini, Marco, Bernardi, Flavia, Forget, Antoine, Blümel, Lena, Talbot, Julie, Picard, Daniel, Qin, Nan, Cancila, Gabriele, Gao, Qingsong, Nath, Soumav, Koumba, Idriss Mahoungou, Wolter, Marietta, Kuonen, François, Langini, Maike, Beez, Thomas, Munoz, Christopher, Pauck, David, Marquardt, Viktoria, Yu, Hua, Souphron, Judith, Korsch, Mascha, Mölders, Christina, Berger, Daniel, Göbbels, Sarah, Meyer, Frauke-Dorothee, Scheffler, Björn, Rotblat, Barak, Diederichs, Sven, Ramaswamy, Vijay, Suzuki, Hiromishi, Oro, Anthony, Stühler, Kai, Stefanski, Anja, Fischer, Ute, Leprivier, Gabriel, Willbold, Dieter, Steger, Gerhard, Buell, Alexander, Kool, Marcel, Lichter, Peter, Pfister, Stefan M., Northcott, Paul A., Taylor, Michael D., Borkhardt, Arndt, Reifenberger, Guido, Ayrault, Olivier, and Remke, Marc
Abstract: Most lncRNAs display species-specific expression patterns suggesting that animal models of cancer may only incompletely recapitulate the regulatory crosstalk between lncRNAs and oncogenic pathways in humans. Among these pathways, Sonic Hedgehog (SHH) signaling is aberrantly activated in several human cancer entities. We unravel that aberrant expression of the primate-specific lncRNA HedgeHog Interacting Protein-AntiSense 1 (HHIP-AS1) is a hallmark of SHH-driven tumors including medulloblastoma and atypical teratoid/rhabdoid tumors. HHIP-AS1 is actively transcribed from a bidirectional promoter shared with SHH regulator HHIP. Knockdown of HHIP-AS1 induces mitotic spindle deregulation impairing tumorigenicity in vitro and in vivo. Mechanistically, HHIP-AS1 binds directly to the mRNA of cytoplasmic dynein 1 intermediate chain 2 (DYNC1I2) and attenuates its degradation by hsa-miR-425-5p. We uncover that neither HHIP-AS1 nor the corresponding regulatory element in DYNC1I2 are evolutionary conserved in mice. Taken together, we discover an lncRNA-mediated mechanism that enables the pro-mitotic effects of SHH pathway activation in human tumors.
Published: 2022

3. Medulloblastoma uses GABA transaminase to survive in the cerebrospinal fluid microenvironment and promote leptomeningeal dissemination.

Author: Martirosian, Vahan, Martirosian, Vahan, Deshpande, Krutika, Zhou, Hao, Shen, Keyue, Smith, Kyle, Northcott, Paul, Lin, Michelle, Stepanosyan, Vazgen, Das, Diganta, Remsik, Jan, Isakov, Danielle, Boire, Adrienne, De Feyter, Henk, Hurth, Kyle, Li, Shaobo, Wiemels, Joseph, Nakamura, Brooke, Shao, Ling, Danilov, Camelia, Chen, Thomas, Neman, Josh, Martirosian, Vahan, Martirosian, Vahan, Deshpande, Krutika, Zhou, Hao, Shen, Keyue, Smith, Kyle, Northcott, Paul, Lin, Michelle, Stepanosyan, Vazgen, Das, Diganta, Remsik, Jan, Isakov, Danielle, Boire, Adrienne, De Feyter, Henk, Hurth, Kyle, Li, Shaobo, Wiemels, Joseph, Nakamura, Brooke, Shao, Ling, Danilov, Camelia, Chen, Thomas, and Neman, Josh
Abstract: Medulloblastoma (MB) is a malignant pediatric brain tumor arising in the cerebellum. Although abnormal GABAergic receptor activation has been described in MB, studies have not yet elucidated the contribution of receptor-independent GABA metabolism to MB pathogenesis. We find primary MB tumors globally display decreased expression of GABA transaminase (ABAT), the protein responsible for GABA metabolism, compared with normal cerebellum. However, less aggressive WNT and SHH subtypes express higher ABAT levels compared with metastatic G3 and G4 tumors. We show that elevated ABAT expression results in increased GABA catabolism, decreased tumor cell proliferation, and induction of metabolic and histone characteristics mirroring GABAergic neurons. Our studies suggest ABAT expression fluctuates depending on metabolite changes in the tumor microenvironment, with nutrient-poor conditions upregulating ABAT expression. We find metastatic MB cells require ABAT to maintain viability in the metabolite-scarce cerebrospinal fluid by using GABA as an energy source substitute, thereby facilitating leptomeningeal metastasis formation.
Published: 2021

4. Medulloblastoma uses GABA transaminase to survive in the cerebrospinal fluid microenvironment and promote leptomeningeal dissemination.

Author: Martirosian, Vahan, Martirosian, Vahan, Deshpande, Krutika, Zhou, Hao, Shen, Keyue, Smith, Kyle, Northcott, Paul, Lin, Michelle, Stepanosyan, Vazgen, Das, Diganta, Remsik, Jan, Isakov, Danielle, Boire, Adrienne, De Feyter, Henk, Hurth, Kyle, Li, Shaobo, Wiemels, Joseph, Nakamura, Brooke, Shao, Ling, Danilov, Camelia, Chen, Thomas, Neman, Josh, Martirosian, Vahan, Martirosian, Vahan, Deshpande, Krutika, Zhou, Hao, Shen, Keyue, Smith, Kyle, Northcott, Paul, Lin, Michelle, Stepanosyan, Vazgen, Das, Diganta, Remsik, Jan, Isakov, Danielle, Boire, Adrienne, De Feyter, Henk, Hurth, Kyle, Li, Shaobo, Wiemels, Joseph, Nakamura, Brooke, Shao, Ling, Danilov, Camelia, Chen, Thomas, and Neman, Josh
Abstract: Medulloblastoma (MB) is a malignant pediatric brain tumor arising in the cerebellum. Although abnormal GABAergic receptor activation has been described in MB, studies have not yet elucidated the contribution of receptor-independent GABA metabolism to MB pathogenesis. We find primary MB tumors globally display decreased expression of GABA transaminase (ABAT), the protein responsible for GABA metabolism, compared with normal cerebellum. However, less aggressive WNT and SHH subtypes express higher ABAT levels compared with metastatic G3 and G4 tumors. We show that elevated ABAT expression results in increased GABA catabolism, decreased tumor cell proliferation, and induction of metabolic and histone characteristics mirroring GABAergic neurons. Our studies suggest ABAT expression fluctuates depending on metabolite changes in the tumor microenvironment, with nutrient-poor conditions upregulating ABAT expression. We find metastatic MB cells require ABAT to maintain viability in the metabolite-scarce cerebrospinal fluid by using GABA as an energy source substitute, thereby facilitating leptomeningeal metastasis formation.
Published: 2021

5. Medulloblastomics revisited : biological and clinical insights from thousands of patients

Author: Hovestadt, Volker, Ayrault, Olivier, Johansson Swartling, Fredrik K., Robinson, Giles W., Pfister, Stefan M., Northcott, Paul A., Hovestadt, Volker, Ayrault, Olivier, Johansson Swartling, Fredrik K., Robinson, Giles W., Pfister, Stefan M., and Northcott, Paul A.
Abstract: Medulloblastoma, a malignant brain tumour primarily diagnosed during childhood, has recently been the focus of intensive molecular profiling efforts, profoundly advancing our understanding of biologically and clinically heterogeneous disease subgroups. Genomic, epigenomic, transcriptomic and proteomic landscapes have now been mapped for an unprecedented number of bulk samples from patients with medulloblastoma and, more recently, for single medulloblastoma cells. These efforts have provided pivotal new insights into the diverse molecular mechanisms presumed to drive tumour initiation, maintenance and recurrence across individual subgroups and subtypes. Translational opportunities stemming from this knowledge are continuing to evolve, providing a framework for improved diagnostic and therapeutic interventions. In this Review, we summarize recent advances derived from this continued molecular characterization of medulloblastoma and contextualize this progress towards the deployment of more effective, molecularly informed treatments for affected patients.
Published: 2020
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6. Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma.

Author: Nobre, Liana, Nobre, Liana, Zapotocky, Michal, Khan, Sara, Fukuoka, Kohei, Fonseca, Adriana, McKeown, Tara, Sumerauer, David, Vicha, Ales, Grajkowska, Wieslawa A, Trubicka, Joanna, Li, Kay Ka Wai, Ng, Ho-Keung, Massimi, Luca, Lee, Ji Yeoun, Kim, Seung-Ki, Zelcer, Shayna, Vasiljevic, Alexandre, Faure-Conter, Cécile, Hauser, Peter, Lach, Boleslaw, van Veelen-Vincent, Marie-Lise, French, Pim J, Van Meir, Erwin G, Weiss, William A, Gupta, Nalin, Pollack, Ian F, Hamilton, Ronald L, Nageswara Rao, Amulya A, Giannini, Caterina, Rubin, Joshua B, Moore, Andrew S, Chambless, Lola B, Vibhakar, Rajeev, Ra, Young Shin, Massimino, Maura, McLendon, Roger E, Wheeler, Helen, Zollo, Massimo, Ferruci, Veronica, Kumabe, Toshihiro, Faria, Claudia C, Sterba, Jaroslav, Jung, Shin, López-Aguilar, Enrique, Mora, Jaume, Carlotti, Carlos G, Olson, James M, Leary, Sarah, Cain, Jason, Krskova, Lenka, Zamecnik, Josef, Hawkins, Cynthia E, Tabori, Uri, Huang, Annie, Bartels, Ute, Northcott, Paul A, Taylor, Michael D, Yip, Stephen, Hansford, Jordan R, Bouffet, Eric, Ramaswamy, Vijay, Nobre, Liana, Nobre, Liana, Zapotocky, Michal, Khan, Sara, Fukuoka, Kohei, Fonseca, Adriana, McKeown, Tara, Sumerauer, David, Vicha, Ales, Grajkowska, Wieslawa A, Trubicka, Joanna, Li, Kay Ka Wai, Ng, Ho-Keung, Massimi, Luca, Lee, Ji Yeoun, Kim, Seung-Ki, Zelcer, Shayna, Vasiljevic, Alexandre, Faure-Conter, Cécile, Hauser, Peter, Lach, Boleslaw, van Veelen-Vincent, Marie-Lise, French, Pim J, Van Meir, Erwin G, Weiss, William A, Gupta, Nalin, Pollack, Ian F, Hamilton, Ronald L, Nageswara Rao, Amulya A, Giannini, Caterina, Rubin, Joshua B, Moore, Andrew S, Chambless, Lola B, Vibhakar, Rajeev, Ra, Young Shin, Massimino, Maura, McLendon, Roger E, Wheeler, Helen, Zollo, Massimo, Ferruci, Veronica, Kumabe, Toshihiro, Faria, Claudia C, Sterba, Jaroslav, Jung, Shin, López-Aguilar, Enrique, Mora, Jaume, Carlotti, Carlos G, Olson, James M, Leary, Sarah, Cain, Jason, Krskova, Lenka, Zamecnik, Josef, Hawkins, Cynthia E, Tabori, Uri, Huang, Annie, Bartels, Ute, Northcott, Paul A, Taylor, Michael D, Yip, Stephen, Hansford, Jordan R, Bouffet, Eric, and Ramaswamy, Vijay
Abstract: Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses.
Published: 2020

7. Pan-cancer analysis of whole genomes

Author: Campbell, Peter J., Getz, Gad, Korbel, Jan O., Stuart, Joshua M., Jennings, Jennifer L., Stein, Lincoln D., Perry, Marc D., Nahal-Bose, Hardeep K., Ouellette, B. F. Francis, Li, Constance H., Rheinbay, Esther, Nielsen, G. Petur, Sgroi, Dennis C., Wu, Chin-Lee, Faquin, William C., Deshpande, Vikram, Boutros, Paul C., Lazar, Alexander J., Hoadley, Katherine A., Louis, David N., Dursi, L. Jonathan, Yung, Christina K., Bailey, Matthew H., Saksena, Gordon, Raine, Keiran M., Buchhalter, Ivo, Kleinheinz, Kortine, Schlesner, Matthias, Zhang, Junjun, Wang, Wenyi, Wheeler, David A., Ding, Li, Simpson, Jared T., O'Connor, Brian D., Yakneen, Sergei, Ellrott, Kyle, Miyoshi, Naoki, Butler, Adam P., Royo, Romina, Shorser, Solomon, I, Vazquez, Miguel, Rausch, Tobias, Tiao, Grace, Waszak, Sebastian M., Rodriguez-Martin, Bernardo, Shringarpure, Suyash, Wu, Dai-Ying, Demidov, German M., Delaneau, Olivier, Hayashi, Shuto, Imoto, Seiya, Habermann, Nina, Segre, Ayellet, V, Garrison, Erik, Cafferkey, Andy, Alvarez, Eva G., Maria Heredia-Genestar, Jose, Muyas, Francesc, Drechsel, Oliver, Bruzos, Alicia L., Temes, Javier, Zamora, Jorge, Baez-Ortega, Adrian, Kim, Hyung-Lae, Mashl, R. Jay, Ye, Kai, DiBiase, Anthony, Huang, Kuan-lin, Letunic, Ivica, McLellan, Michael D., Newhouse, Steven J., Shmaya, Tal, Kumar, Sushant, Wedge, David C., Wright, Mark H., Yellapantula, Venkata D., Gerstein, Mark, Khurana, Ekta, Marques-Bonet, Tomas, Navarro, Arcadi, Bustamante, Carlos D., Siebert, Reiner, Nakagawa, Hidewaki, Easton, Douglas F., Ossowski, Stephan, Tubio, Jose M. C., De La Vega, Francisco M., Estivill, Xavier, Yuen, Denis, Mihaiescu, George L., Omberg, Larsson, Ferretti, Vincent, Sabarinathan, Radhakrishnan, Pich, Oriol, Gonzalez-Perez, Abel, Weiner, Amaro Taylor, Fittall, Matthew W., Demeulemeester, Jonas, Tarabichi, Maxime, Roberts, Nicola D., Van Loo, Peter, Cortes-Ciriano, Isidro, Urban, Lara, Park, Peter, Pitkaenen, Esa, Li, Yilong, Saini, Natalie, Klimczak, Leszek J., Weischenfeldt, Joachim, Sidiropoulos, Nikos, Alexandrov, Ludmil B., Rabionet, Raquel, Escaramis, Georgia, Bosio, Mattia, Holik, Aliaksei Z., Susak, Hana, Prasad, Aparna, Erkek, Serap, Calabrese, Claudia, Raeder, Benjamin, Harrington, Eoghan, Mayes, Simon, Turner, Daniel, Juul, Sissel, Roberts, Steven A., Song, Lei, Koster, Roelof, Mirabello, Lisa, Hua, Xing, Tanskanen, Tomas J., Tojo, Marta, Chen, Jieming, Aaltonen, Lauri A., Ratsch, Gunnar, Schwarz, Roland F., Butte, Atul J., Brazma, Alvis, Chanock, Stephen J., Chatterjee, Nilanjan, Stegle, Oliver, Harismendy, Olivier, Bova, G. Steven, Gordenin, Dmitry A., Haan, David, Sieverling, Lina, Feuerbach, Lars, Chalmers, Don, Joly, Yann, Knoppers, Bartha, Molnar-Gabor, Fruzsina, Phillips, Mark, Thorogood, Adrian, Townend, David, Goldman, Mary, Fonseca, Nuno A., Xiang, Qian, Craft, Brian, Pineiro-Yanez, Elena, Munoz, Alfonso, Petryszak, Robert, Fullgrabe, Anja, Al-Shahrour, Fatima, Keays, Maria, Haussler, David, Weinstein, John, Huber, Wolfgang, Valencia, Alfonso, Papatheodorou, Irene, Zhu, Jingchun, Fan, Yu, Torrents, David, Bieg, Matthias, Chen, Ken, Chong, Zechen, Cibulskis, Kristian, Eils, Roland, Fulton, Robert S., Gelpi, Josep L., Gonzalez, Santiago, Gut, Ivo G., Hach, Faraz, Heinold, Michael, Hu, Taobo, Huang, Vincent, Hutter, Barbara, Jaeger, Natalie, Jung, Jongsun, Kumar, Yogesh, Lalansingh, Christopher, Leshchiner, Ignaty, Livitz, Dimitri, Ma, Eric Z., Maruvka, Yosef E., Milovanovic, Ana, Nielsen, Morten Muhlig, Paramasivam, Nagarajan, Pedersen, Jakob Skou, Puiggros, Montserrat, Sahinalp, S. Cenk, Sarrafi, Iman, Stewart, Chip, Stobbe, Miranda D., Wala, Jeremiah A., Wang, Jiayin, Wendl, Michael, Werner, Johannes, Wu, Zhenggang, Xue, Hong, Yamaguchi, Takafumi N., Yellapantula, Venkata, Davis-Dusenbery, Brandi N., Grossman, Robert L., Kim, Youngwook, Heinold, Michael C., Hinton, Jonathan, Jones, David R., Menzies, Andrew, Stebbings, Lucy, Hess, Julian M., Rosenberg, Mara, Dunford, Andrew J., Gupta, Manaswi, Imielinski, Marcin, Meyerson, Matthew, Beroukhim, Rameen, Reimand, Juri, Dhingra, Priyanka, Favero, Francesco, Dentro, Stefan, Wintersinger, Jeff, Rudneva, Vasilisa, Park, Ji Wan, Hong, Eun Pyo, Heo, Seong Gu, Kahles, Andre, Soulette, Cameron M., Shiraishi, Yuichi, Liu, Fenglin, He, Yao, Demircioglu, Deniz, Davidson, Natalie R., Greger, Liliana, Li, Siliang, Liu, Dongbing, Stark, Stefan G., Zhang, Fan, Amin, Samirkumar B., Bailey, Peter, Chateigner, Aurelien, Frenkel-Morgenstern, Milana, Hou, Yong, Huska, Matthew R., Kilpinen, Helena, Lamaze, Fabien C., Li, Chang, Li, Xiaobo, Li, Xinyue, Liu, Xingmin, Marin, Maximillian G., Markowski, Julia, Nandi, Tannistha, Ojesina, Akinyemi, I, Pan-Hammarstrom, Qiang, Park, Peter J., Pedamallu, Chandra Sekhar, Su, Hong, Tan, Patrick, Teh, Bin Tean, Wang, Jian, Xiong, Heng, Ye, Chen, Yung, Christina, Zhang, Xiuqing, Zheng, Liangtao, Zhu, Shida, Awadalla, Philip, Creighton, Chad J., Wu, Kui, Yang, Huanming, Goke, Jonathan, Zhang, Zemin, Brooks, Angela N., Martincorena, Inigo, Rubio-Perez, Carlota, Juul, Malene, Schumacher, Steven, Shapira, Ofer, Tamborero, David, Mularoni, Loris, Hornshoj, Henrik, Deu-Pons, Jordi, Muinos, Ferran, Bertl, Johanna, Guo, Qianyun, Bazant, Wojciech, Barrera, Elisabet, Al-Sedairy, Sultan T., Aretz, Axel, Bell, Cindy, Betancourt, Miguel, Buchholz, Christiane, Calvo, Fabien, Chomienne, Christine, Dunn, Michael, Edmonds, Stuart, Green, Eric, Gupta, Shailja, Hutter, Carolyn M., Jegalian, Karine, Jones, Nic, Lu, Youyong, Nakagama, Hitoshi, Nettekoven, Gerd, Planko, Laura, Scott, David, Shibata, Tatsuhiro, Shimizu, Kiyo, Stratton, Michael R., Yugawa, Takashi, Tortora, Giampaolo, VijayRaghavan, K., Zenklusen, Jean C., Knoppers, Bartha M., Aminou, Brice, Bartolome, Javier, Boroevich, Keith A., Boyce, Rich, Buchanan, Alex, Byrne, Niall J., Chen, Zhaohong, Cho, Sunghoon, Choi, Wan, Clapham, Peter, Dow, Michelle T., Dursi, Lewis Jonathan, Eils, Juergen, Farcas, Claudiu, Fayzullaev, Nodirjon, Flicek, Paul, Heath, Allison P., Hofmann, Oliver, Hong, Jongwhi H., Hudson, Thomas J., Huebschmann, Daniel, Ivkovic, Sinisa, Jeon, Seung-Hyup, Jiao, Wei, Kabbe, Rolf, Kerssemakers, Jules N. A., Kim, Hyunghwan, Kim, Jihoon, Koscher, Michael, Koures, Antonios, Kovacevic, Milena, Lawerenz, Chris, Liu, Jia, Mijalkovic, Sanja, Mijalkovic-Lazic, Ana Mijalkovic, Miyano, Satoru, Nastic, Mia, Nicholson, Jonathan, Ocana, David, Ohi, Kazuhiro, Ohno-Machado, Lucila, Pihl, Todd D., Prinz, Manuel, Radovic, Petar, Short, Charles, Sofia, Heidi J., Spring, Jonathan, Struck, Adam J., Tijanic, Nebojsa, Vicente, David, Wang, Zhining, Williams, Ashley, Woo, Youngchoon, Wright, Adam J., Yang, Liming, Hamilton, Mark P., Johnson, Todd A., Kahraman, Abdullah, Kellis, Manolis, Polak, Paz, Sallari, Richard, Sinnott-Armstrong, Nasa, von Mering, Christian, Beltran, Sergi, Gerhard, Daniela S., Gut, Marta, Trotta, Jean-Remi, Whalley, Justin P., Niu, Beifang, Espiritu, Shadrielle M. G., Gao, Shengjie, Huang, Yi, Lalansingh, Christopher M., Teague, Jon W., Wendl, Michael C., Abascal, Federico, Bader, Gary D., Bandopadhayay, Pratiti, Barenboim, Jonathan, Brunak, Soren, Fita, Joana Carlevaro, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Choi, Jung Kyoon, Diamanti, Klev, Fink, J. Lynn, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W., Haradhvala, Nicholas J., Harmanci, Arif O., Helmy, Mohamed, Herrmann, Carl, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Isaev, Keren, Izarzugaza, Jose M. G., Johnson, Rory, Juul, Randi Istrup, Kim, Jaegil, Kim, Jong K., Komorowski, Jan, Lanzos, Andres, Larsson, Erik, Lee, Donghoon, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Fundichely, Alexander Martinez, McGillivray, Patrick D., Meyerson, William, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pons, Tirso, Pulido-Tamayo, Sergio, Reyes Salazar, Iker, Reyna, Matthew A., Rubin, Mark A., Salichos, Leonidas, Sander, Chris, Schumacher, Steven E., Shackleton, Mark, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Tsunoda, Tatsuhiko, Umer, Husen M., Uuskula-Reimand, Liis, Verbeke, Lieven P. C., Wadelius, Claes, Wadi, Lina, Warrell, Jonathan, Wu, Guanming, Yu, Jun, Zhang, Jing, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, Lawrence, Michael S., Raphael, Benjamin J., Bailey, Peter J., Craft, David, Goldman, Mary J., Aburatani, Hiroyuki, Binder, Hans, Dinh, Huy Q., Heath, Simon C., Hoffmann, Steve, Imbusch, Charles David, Kretzmer, Helene, Laird, Peter W., Martin-Subero, Jose, I, Nagae, Genta, Shen, Hui, Wang, Qi, Weichenhan, Dieter, Zhou, Wanding, Berman, Benjamin P., Brors, Benedikt, Plass, Christoph, Akdemir, Kadir C., Bowtell, David D. L., Burns, Kathleen H., Busanovich, John, Chan, Kin, Dueso-Barroso, Ana, Edwards, Paul A., Etemadmoghadam, Dariush, Haber, James E., Jones, David T. W., Ju, Young Seok, Kazanov, Marat D., Koh, Youngil, Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Lynch, Andy G., Macintyre, Geoff, Markowetz, Florian, Navarro, Fabio C. P., Pearson, John, V, Rippe, Karsten, Scully, Ralph, Villasante, Izar, Waddell, Nicola, Yang, Lixing, Yao, Xiaotong, Yoon, Sung-Soo, Zhang, Cheng-Zhong, Bergstrom, Erik N., Boot, Arnoud, Covington, Kyle, Fujimoto, Akihiro, Huang, Mi Ni, Islam, S. M. Ashiqul, McPherson, John R., Morganella, Sandro, Mustonen, Ville, Ng, Alvin Wei Tian, Prokopec, Stephenie D., Vazquez-Garcia, Ignacio, Wu, Yang, Yousif, Fouad, Yu, Willie, Rozen, Steven G., Rudneva, Vasilisa A., Shringarpure, Suyash S., Turner, Daniel J., Xia, Tian, Atwal, Gurnit, Chang, David K., Cooke, Susanna L., Faltas, Bishoy M., Haider, Syed, Kaiser, Vera B., Karlic, Rosa, Kato, Mamoru, Kubler, Kirsten, Margolin, Adam, Martin, Sancha, Nik-Zainal, Serena, P'ng, Christine, Semple, Colin A., Smith, Jaclyn, Sun, Ren X., Thai, Kevin, Wright, Derek W., Yuan, Ke, Biankin, Andrew, V, Garraway, Levi, Grimmond, Sean M., Adams, David J., Anur, Pavana, Cao, Shaolong, Christie, Elizabeth L., Cmero, Marek, Cun, Yupeng, Dawson, Kevin J., Dentro, Stefan C., Deshwar, Amit G., Donmez, Nilgun, Drews, Ruben M., Gerstung, Moritz, Ha, Gavin, Haase, Kerstin, Jerman, Lara, Ji, Yuan, Jolly, Clemency, Lee, Juhee, Lee-Six, Henry, Malikic, Salem, Mitchell, Thomas J., Morris, Quaid D., Oesper, Layla, Peifer, Martin, Peto, Myron, Rosebrock, Daniel, Rubanova, Yulia, Salcedo, Adriana, Sengupta, Subhajit, Shi, Ruian, Shin, Seung Jun, Spiro, Oliver, Vembu, Shankar, Wintersinger, Jeffrey A., Yang, Tsun-Po, Yu, Kaixian, Zhu, Hongtu, Spellman, Paul T., Weinstein, John N., Chen, Yiwen, Fujita, Masashi, Han, Leng, Hasegawa, Takanori, Komura, Mitsuhiro, Li, Jun, Mizuno, Shinichi, Shimizu, Eigo, Wang, Yumeng, Xu, Yanxun, Yamaguchi, Rui, Yang, Fan, Yang, Yang, Yoon, Christopher J., Yuan, Yuan, Liang, Han, Alawi, Malik, Borozan, Ivan, Brewer, Daniel S., Cooper, Colin S., Desai, Nikita, Grundhoff, Adam, Iskar, Murat, Su, Xiaoping, Zapatka, Marc, Lichter, Peter, Alsop, Kathryn, Bruxner, Timothy J. C., Christ, Angelika N., Cordner, Stephen M., Cowin, Prue A., Drapkin, Ronny, Fereday, Sian, George, Joshy, Hamilton, Anne, Holmes, Oliver, Hung, Jillian A., Kassahn, Karin S., Kazakoff, Stephen H., Kennedy, Catherine J., Leonard, Conrad R., Mileshkin, Linda, Miller, David K., Arnau, Gisela Mir, Mitchell, Chris, Newell, Felicity, Nones, Katia, Patch, Ann-Marie, Quinn, Michael C., Taylor, Darrin F., Thorne, Heather, Traficante, Nadia, Vedururu, Ravikiran, Waddell, Nick M., Waring, Paul M., Wood, Scott, Xu, Qinying, DeFazio, Anna, Anderson, Matthew J., Antonello, Davide, Barbour, Andrew P., Bassi, Claudio, Bersani, Samantha, Cataldo, Ivana, Chantrill, Lorraine A., Chiew, Yoke-Eng, Chou, Angela, Cingarlini, Sara, Cloonan, Nicole, Corbo, Vincenzo, Davi, Maria Vittoria, Duthie, Fraser R., Gill, Anthony J., Graham, Janet S., Harliwong, Ivon, Jamieson, Nigel B., Johns, Amber L., Kench, James G., Landoni, Luca, Lawlor, Rita T., Mafficini, Andrea, Merrett, Neil D., Miotto, Marco, Musgrove, Elizabeth A., Nagrial, Adnan M., Oien, Karin A., Pajic, Marina, Pinese, Mark, Robertson, Alan J., Rooman, Ilse, Rusev, Borislav C., Samra, Jaswinder S., Scardoni, Maria, Scarlett, Christopher J., Scarpa, Aldo, Sereni, Elisabetta, Sikora, Katarzyna O., Simbolo, Michele, Taschuk, Morgan L., Toon, Christopher W., Vicentini, Caterina, Wu, Jianmin, Zeps, Nikolajs, Behren, Andreas, Burke, Hazel, Cebon, Jonathan, Dagg, Rebecca A., De Paoli-Iseppi, Ricardo, Dutton-Regester, Ken, Field, Matthew A., Fitzgerald, Anna, Hersey, Peter, Jakrot, Valerie, Johansson, Peter A., Kakavand, Hojabr, Kefford, Richard F., Lau, Loretta M. S., Long, Georgina, V, Pickett, Hilda A., Pritchard, Antonia L., Pupo, Gulietta M., Saw, Robyn P. M., Schramm, Sarah-Jane, Shang, Catherine A., Shang, Ping, Spillane, Andrew J., Stretch, Jonathan R., Tembe, Varsha, Thompson, John F., Vilain, Ricardo E., Wilmott, James S., Yang, Jean Y., Hayward, Nicholas K., Mann, Graham J., Scolyer, Richard A., Bartlett, John, Bavi, Prashant, Chadwick, Dianne E., Chan-Seng-Yue, Michelle, Cleary, Sean, Connor, Ashton A., Czajka, Karolina, Denroche, Robert E., Dhani, Neesha C., Eagles, Jenna, Gallinger, Steven, Grant, Robert C., Hedley, David, Hollingsworth, Michael A., Jang, Gun Ho, Johns, Jeremy, Kalimuthu, Sangeetha, Liang, Sheng-Ben, Lungu, Ilinca, Luo, Xuemei, Mbabaali, Faridah, McPherson, Treasa A., Miller, Jessica K., Moore, Malcolm J., Notta, Faiyaz, Pasternack, Danielle, Petersen, Gloria M., Roehrl, Michael H. A., Sam, Michelle, Selander, Iris, Serra, Stefano, Shahabi, Sagedeh, Thayer, Sarah P., Timms, Lee E., Wilson, Gavin W., Wilson, Julie M., Wouters, Bradly G., McPherson, John D., Beck, Timothy A., Bhandari, Vinayak, Collins, Colin C., Fleshner, Neil E., Fox, Natalie S., Fraser, Michael, Heisler, Lawrence E., Lalonde, Emilie, Livingstone, Julie, Meng, Alice, Sabelnykova, Veronica Y., Shiah, Yu-Jia, Van Der Kwast, Theodorus, Bristow, Robert G., Ding, Shuai, Fan, Daiming, Li, Lin, Nie, Yongzhan, Xiao, Xiao, Xing, Rui, Yang, Shanlin, Yu, Yingyan, Zhou, Yong, Banks, Rosamonde E., Bourque, Guillaume, Brennan, Paul, Letourneau, Louis, Riazalhosseini, Yasser, Scelo, Ghislaine, Vasudev, Naveen, Viksna, Juris, Lathrop, Mark, Tost, Jorg, Ahn, Sung-Min, Aparicio, Samuel, Arnould, Laurent, Aure, M. R., Bhosle, Shriram G., Birney, Ewan, Borg, Ake, Boyault, Sandrine, Brinkman, Arie B., Brock, Jane E., Broeks, Annegien, Borresen-Dale, Anne-Lise, Caldas, Carlos, Chin, Suet-Feung, Davies, Helen, Desmedt, Christine, Dirix, Luc, Dronov, Serge, Ehinger, Anna, Eyfjord, Jorunn E., Fatima, Aquila, Foekens, John A., Futreal, P. Andrew, Garred, Oystein, Giri, Dilip D., Glodzik, Dominik, Grabau, Dorthe, Hilmarsdottir, Holmfridur, Hooijer, Gerrit K., Jacquemier, Jocelyne, Jang, Se Jin, Jonasson, Jon G., Jonkers, Jos, Kim, Hyung-Yong, King, Tari A., Knappskog, Stian, Kong, Gu, Krishnamurthy, Savitri, Lakhani, Sunil R., Langerod, Anita, Larsimont, Denis, Lee, Hee Jin, Lee, Jeong-Yeon, Lee, Ming Ta Michael, Lingjaerde, Ole Christian, MacGrogan, Gaetan, Martens, John W. M., O'Meara, Sarah, Pauporte, Iris, Pinder, Sarah, Pivot, Xavier, Provenzano, Elena, Purdie, Colin A., Ramakrishna, Manasa, Ramakrishnan, Kamna, Reis-Filho, Jorge, Richardson, Andrea L., Ringner, Markus, Rodriguez, Javier Bartolome, Rodriguez-Gonzalez, F. German, Romieu, Gilles, Salgado, Roberto, Sauer, Torill, Shepherd, Rebecca, Sieuwerts, Anieta M., Simpson, Peter T., Smid, Marcel, Sotiriou, Christos, Span, Paul N., Stefansson, Olafur Andri, Stenhouse, Alasdair, Stunnenberg, Henk G., Sweep, Fred, Tan, Benita Kiat Tee, Thomas, Gilles, Thompson, Alastair M., Tommasi, Stefania, Treilleux, Isabelle, Tutt, Andrew, Ueno, Naoto T., Van Laere, Steven, Van den Eynden, Gert G., Vermeulen, Peter, Viari, Alain, Vincent-Salomon, Anne, Wong, Bernice H., Yates, Lucy, Zou, Xueqing, van Deurzen, Carolien H. M., van de Vijver, Marc J., van't Veer, Laura, Ammerpohl, Ole, Aukema, Sietse, Bergmann, Anke K., Bernhart, Stephan H., Borkhardt, Arndt, Borst, Christoph, Burkhardt, Birgit, Claviez, Alexander, Goebler, Maria Elisabeth, Haake, Andrea, Haas, Siegfried, Hansmann, Martin, Hoell, Jessica, I, Hummel, Michael, Karsch, Dennis, Klapper, Wolfram, Kneba, Michael, Kreuz, Markus, Kube, Dieter, Kueppers, Ralf, Lenze, Dido, Loeffler, Markus, Lopez, Cristina, Mantovani-Loeffler, Luisa, Moeller, Peter, Ott, German, Radlwimmer, Bernhard, Richter, Julia, Rohde, Marius, Rosenstiel, Philip C., Rosenwald, Andreas, Schilhabel, Markus B., Schreiber, Stefan, Stadler, Peter F., Staib, Peter, Stilgenbauer, Stephan, Sungalee, Stephanie, Szczepanowski, Monika, Toprak, Umut H., Truemper, Lorenz H. P., Wagener, Rabea, Zenz, Thorsten, Hovestadt, Volker, von Kalle, Christof, Kool, Marcel, Korshunov, Andrey, Landgraf, Pablo, Lehrach, Hans, Northcott, Paul A., Pfister, Stefan M., Reifenberger, Guido, Warnatz, Hans-Joerg, Wolf, Stephan, Yaspo, Marie-Laure, Assenov, Yassen, Gerhauser, Clarissa, Minner, Sarah, Schlomm, Thorsten, Simon, Ronald, Sauter, Guido, Sueltmann, Holger, Biswas, Nidhan K., Maitra, Arindam, Majumder, Partha P., Sarin, Rajiv, Barbi, Stefano, Bonizzato, Giada, Cantu, Cinzia, Dei Tos, Angelo P., Fassan, Matteo, Grimaldi, Sonia, Luchini, Claudio, Malleo, Giuseppe, Marchegiani, Giovanni, Milella, Michele, Paiella, Salvatore, Pea, Antonio, Pederzoli, Paolo, Ruzzenente, Andrea, Salvia, Roberto, Sperandio, Nicola, Arai, Yasuhito, Hama, Natsuko, Hiraoka, Nobuyoshi, Hosoda, Fumie, Nakamura, Hiromi, Ojima, Hidenori, Okusaka, Takuji, Totoki, Yasushi, Urushidate, Tomoko, Fukayama, Masashi, Ishikawa, Shumpei, Katai, Hitoshi, Katoh, Hiroto, Komura, Daisuke, Rokutan, Hirofumi, Saito-Adachi, Mihoko, Suzuki, Akihiro, Taniguchi, Hirokazu, Tatsuno, Kenji, Ushiku, Tetsuo, Yachida, Shinichi, Yamamoto, Shogo, Aikata, Hiroshi, Arihiro, Koji, Ariizumi, Shun-ichi, Chayama, Kazuaki, Furuta, Mayuko, Gotoh, Kunihito, Hayami, Shinya, Hirano, Satoshi, Kawakami, Yoshiiku, Maejima, Kazuhiro, Nakamura, Toru, Nakano, Kaoru, Ohdan, Hideki, Sasaki-Oku, Aya, Tanaka, Hiroko, Ueno, Masaki, Yamamoto, Masakazu, Yamaue, Hiroki, Choo, Su Pin, Cutcutache, Ioana, Khuntikeo, Narong, Ong, Choon Kiat, Pairojkul, Chawalit, Popescu, Irinel, Ahn, Keun Soo, Aymerich, Marta, Lopez-Guillermo, Armando, Lopez-Otin, Carlos, Puente, Xose S., Campo, Elias, Amary, Fernanda, Baumhoer, Daniel, Behjati, Sam, Bjerkehagen, Bodil, Futreal, P. A., Myklebost, Ola, Pillay, Nischalan, Tarpey, Patrick, Tirabosco, Roberto, Zaikova, Olga, Flanagan, Adrienne M., Boultwood, Jacqueline, Bowen, David T., Cazzola, Mario, Green, Anthony R., Hellstrom-Lindberg, Eva, Malcovati, Luca, Nangalia, Jyoti, Papaemmanuil, Elli, Vyas, Paresh, Ang, Yeng, Barr, Hugh, Beardsmore, Duncan, Eldridge, Matthew, Gossage, James, Grehan, Nicola, Hanna, George B., Hayes, Stephen J., Hupp, Ted R., Khoo, David, Lagergren, Jesper, Lovat, Laurence B., MacRae, Shona, O'Donovan, Maria, O'Neill, J. Robert, Parsons, Simon L., Preston, Shaun R., Puig, Sonia, Roques, Tom, Sanders, Grant, Sothi, Sharmila, Tavare, Simon, Tucker, Olga, Turkington, Richard, Underwood, Timothy J., Welch, Ian, Fitzgerald, Rebecca C., Berney, Daniel M., De Bono, Johann S., Cahill, Declan, Camacho, Niedzica, Dennis, Nening M., Dudderidge, Tim, Edwards, Sandra E., Fisher, Cyril, Foster, Christopher S., Ghori, Mohammed, Gill, Pelvender, Gnanapragasam, Vincent J., Gundem, Gunes, Hamdy, Freddie C., Hawkins, Steve, Hazell, Steven, Howat, William, Isaacs, William B., Karaszi, Katalin, Kay, Jonathan D., Khoo, Vincent, Kote-Jarai, Zsofia, Kremeyer, Barbara, Kumar, Pardeep, Lambert, Adam, Leongamornlert, Daniel A., Livni, Naomi, Lu, Yong-Jie, Luxton, Hayley J., Marsden, Luke, Massie, Charlie E., Matthews, Lucy, Mayer, Erik, McDermott, Ultan, Merson, Sue, Neal, David E., Ng, Anthony, Nicol, David, Ogden, Christopher, Rowe, Edward W., Shah, Nimish C., Thomas, Sarah, Thompson, Alan, Verrill, Clare, Visakorpi, Tapio, Warren, Anne Y., Whitaker, Hayley C., Zhang, Hongwei, van As, Nicholas, Eeles, Rosalind A., Abeshouse, Adam, Agrawal, Nishant, Akbani, Rehan, Al Ahmadie, Hikmat, Albert, Monique, Aldape, Kenneth, Ally, Adrian, Appelbaum, Elizabeth L., Armenia, Joshua, Asa, Sylvia, Auman, J. Todd, Balasundaram, Miruna, Balu, Saianand, Barnholtz-Sloan, Jill, Bathe, Oliver F., Baylin, Stephen B., Benz, Christopher, Berchuck, Andrew, Berrios, Mario, Bigner, Darell, Birrer, Michael, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S., Bosenberg, Marcus, Bowlby, Reanne, Boyd, Jeffrey, Broaddus, Russell R., Brock, Malcolm, Brooks, Denise, Bullman, Susan, Caesar-Johnson, Samantha J., Carey, Thomas E., Carlsen, Rebecca, Cerfolio, Robert, Chandan, Vishal S., Chen, Hsiao-Wei, Cherniack, Andrew D., Chien, Jeremy, Cho, Juok, Chuah, Eric, Cibulskis, Carrie, Cope, Leslie, Cordes, Matthew G., Curley, Erin, Czerniak, Bogdan, Danilova, Ludmila, Davis, Ian J., Defreitas, Timothy, Demchok, John A., Dhalla, Noreen, Dhir, Rajiv, Doddapaneni, HarshaVardhan, El-Naggar, Adel, Felau, Ina, Ferguson, Martin L., Finocchiaro, Gaetano, Fong, Kwun M., Frazer, Scott, Friedman, William, Fronick, Catrina C., Fulton, Lucinda A., Gabriel, Stacey B., Gao, Jianjiong, Gehlenborg, Nils, Gershenwald, Jeffrey E., Ghossein, Ronald, Giama, Nasra H., Gibbs, Richard A., Gomez, Carmen, Govindan, Ramaswamy, Hayes, D. Neil, Hegde, Apurva M., Heiman, David, I, Heins, Zachary, Hepperla, Austin J., Holbrook, Andrea, Holt, Robert A., Hoyle, Alan P., Hruban, Ralph H., Hu, Jianhong, Huang, Mei, Huntsman, David, Huse, Jason, Donahue, Christine A. Iacobuzio, Ittmann, Michael, Jayaseelan, Joy C., Jefferys, Stuart R., Jones, Corbin D., Jones, Steven J. M., Juhl, Hartmut, Kang, Koo Jeong, Karlan, Beth, Kasaian, Katayoon, Kebebew, Electron, Kim, Hark Kyun, Korchina, Viktoriya, Kundra, Ritika, Lai, Phillip H., Lander, Eric, Le, Xuan, Lee, Darlene, Levine, Douglas A., Lewis, Lora, Ley, Tim, Li, Haiyan Irene, Lin, Pei, Linehan, W. M., Liu, Fei Fei, Lu, Yiling, Lype, Lisa, Ma, Yussanne, Maglinte, Dennis T., Mardis, Elaine R., Marks, Jeffrey, Marra, Marco A., Matthew, Thomas J., Mayo, Michael, McCune, Karen, Meier, Samuel R., Meng, Shaowu, Mieczkowski, Piotr A., Mikkelsen, Tom, Miller, Christopher A., Mills, Gordon B., Moore, Richard A., Morrison, Carl, Mose, Lisle E., Moser, Catherine D., Mungall, Andrew J., Mungall, Karen, Mutch, David, Muzny, Donna M., Myers, Jerome, Newton, Yulia, Noble, Michael S., O'Donnell, Peter, O'Neill, Brian Patrick, Ochoa, Angelica, Park, Joong-Won, Parker, Joel S., Pass, Harvey, Pastore, Alessandro, Pennell, Nathan A., Perou, Charles M., Petrelli, Nicholas, Potapova, Olga, Rader, Janet S., Ramalingam, Suresh, Rathmell, W. Kimryn, Reuter, Victor, Reynolds, Sheila M., Ringel, Matthew, Roach, Jeffrey, Roberts, Lewis R., Robertson, A. Gordon, Sadeghi, Sara, Saller, Charles, Sanchez-Vega, Francisco, Schadendorf, Dirk, Schein, Jacqueline E., Schmidt, Heather K., Schultz, Nikolaus, Seethala, Raja, Senbabaoglu, Yasin, Shelton, Troy, Shi, Yan, Shih, Juliann, Shmulevich, Ilya, Shriver, Craig, Signoretti, Sabina, Simons, Janae, V, Singer, Samuel, Sipahimalani, Payal, Skelly, Tara J., McCune, Karen Smith, Socci, Nicholas D., Soloway, Matthew G., Sood, Anil K., Tam, Angela, Tan, Donghui, Tarnuzzer, Roy, Thiessen, Nina, Thompson, R. Houston, Thorne, Leigh B., Tsao, Ming, Umbricht, Christopher, Van Den Berg, David J., Van Meir, Erwin G., Veluvolu, Umadevi, Voet, Douglas, Wang, Linghua, Weinberger, Paul, Weisenberger, Daniel J., Wigle, Dennis, Wilkerson, Matthew D., Wilson, Richard K., Winterhoff, Boris, Wiznerowicz, Maciej, Wong, Tina, Wong, Winghing, Xi, Liu, Yau, Christina, Zhang, Hailei, Zhang, Hongxin, Zhang, Jiashan, Campbell, Peter J., Getz, Gad, Korbel, Jan O., Stuart, Joshua M., Jennings, Jennifer L., Stein, Lincoln D., Perry, Marc D., Nahal-Bose, Hardeep K., Ouellette, B. F. Francis, Li, Constance H., Rheinbay, Esther, Nielsen, G. Petur, Sgroi, Dennis C., Wu, Chin-Lee, Faquin, William C., Deshpande, Vikram, Boutros, Paul C., Lazar, Alexander J., Hoadley, Katherine A., Louis, David N., Dursi, L. Jonathan, Yung, Christina K., Bailey, Matthew H., Saksena, Gordon, Raine, Keiran M., Buchhalter, Ivo, Kleinheinz, Kortine, Schlesner, Matthias, Zhang, Junjun, Wang, Wenyi, Wheeler, David A., Ding, Li, Simpson, Jared T., O'Connor, Brian D., Yakneen, Sergei, Ellrott, Kyle, Miyoshi, Naoki, Butler, Adam P., Royo, Romina, Shorser, Solomon, I, Vazquez, Miguel, Rausch, Tobias, Tiao, Grace, Waszak, Sebastian M., Rodriguez-Martin, Bernardo, Shringarpure, Suyash, Wu, Dai-Ying, Demidov, German M., Delaneau, Olivier, Hayashi, Shuto, Imoto, Seiya, Habermann, Nina, Segre, Ayellet, V, Garrison, Erik, Cafferkey, Andy, Alvarez, Eva G., Maria Heredia-Genestar, Jose, Muyas, Francesc, Drechsel, Oliver, Bruzos, Alicia L., Temes, Javier, Zamora, Jorge, Baez-Ortega, Adrian, Kim, Hyung-Lae, Mashl, R. Jay, Ye, Kai, DiBiase, Anthony, Huang, Kuan-lin, Letunic, Ivica, McLellan, Michael D., Newhouse, Steven J., Shmaya, Tal, Kumar, Sushant, Wedge, David C., Wright, Mark H., Yellapantula, Venkata D., Gerstein, Mark, Khurana, Ekta, Marques-Bonet, Tomas, Navarro, Arcadi, Bustamante, Carlos D., Siebert, Reiner, Nakagawa, Hidewaki, Easton, Douglas F., Ossowski, Stephan, Tubio, Jose M. C., De La Vega, Francisco M., Estivill, Xavier, Yuen, Denis, Mihaiescu, George L., Omberg, Larsson, Ferretti, Vincent, Sabarinathan, Radhakrishnan, Pich, Oriol, Gonzalez-Perez, Abel, Weiner, Amaro Taylor, Fittall, Matthew W., Demeulemeester, Jonas, Tarabichi, Maxime, Roberts, Nicola D., Van Loo, Peter, Cortes-Ciriano, Isidro, Urban, Lara, Park, Peter, Pitkaenen, Esa, Li, Yilong, Saini, Natalie, Klimczak, Leszek J., Weischenfeldt, Joachim, Sidiropoulos, Nikos, Alexandrov, Ludmil B., Rabionet, Raquel, Escaramis, Georgia, Bosio, Mattia, Holik, Aliaksei Z., Susak, Hana, Prasad, Aparna, Erkek, Serap, Calabrese, Claudia, Raeder, Benjamin, Harrington, Eoghan, Mayes, Simon, Turner, Daniel, Juul, Sissel, Roberts, Steven A., Song, Lei, Koster, Roelof, Mirabello, Lisa, Hua, Xing, Tanskanen, Tomas J., Tojo, Marta, Chen, Jieming, Aaltonen, Lauri A., Ratsch, Gunnar, Schwarz, Roland F., Butte, Atul J., Brazma, Alvis, Chanock, Stephen J., Chatterjee, Nilanjan, Stegle, Oliver, Harismendy, Olivier, Bova, G. Steven, Gordenin, Dmitry A., Haan, David, Sieverling, Lina, Feuerbach, Lars, Chalmers, Don, Joly, Yann, Knoppers, Bartha, Molnar-Gabor, Fruzsina, Phillips, Mark, Thorogood, Adrian, Townend, David, Goldman, Mary, Fonseca, Nuno A., Xiang, Qian, Craft, Brian, Pineiro-Yanez, Elena, Munoz, Alfonso, Petryszak, Robert, Fullgrabe, Anja, Al-Shahrour, Fatima, Keays, Maria, Haussler, David, Weinstein, John, Huber, Wolfgang, Valencia, Alfonso, Papatheodorou, Irene, Zhu, Jingchun, Fan, Yu, Torrents, David, Bieg, Matthias, Chen, Ken, Chong, Zechen, Cibulskis, Kristian, Eils, Roland, Fulton, Robert S., Gelpi, Josep L., Gonzalez, Santiago, Gut, Ivo G., Hach, Faraz, Heinold, Michael, Hu, Taobo, Huang, Vincent, Hutter, Barbara, Jaeger, Natalie, Jung, Jongsun, Kumar, Yogesh, Lalansingh, Christopher, Leshchiner, Ignaty, Livitz, Dimitri, Ma, Eric Z., Maruvka, Yosef E., Milovanovic, Ana, Nielsen, Morten Muhlig, Paramasivam, Nagarajan, Pedersen, Jakob Skou, Puiggros, Montserrat, Sahinalp, S. Cenk, Sarrafi, Iman, Stewart, Chip, Stobbe, Miranda D., Wala, Jeremiah A., Wang, Jiayin, Wendl, Michael, Werner, Johannes, Wu, Zhenggang, Xue, Hong, Yamaguchi, Takafumi N., Yellapantula, Venkata, Davis-Dusenbery, Brandi N., Grossman, Robert L., Kim, Youngwook, Heinold, Michael C., Hinton, Jonathan, Jones, David R., Menzies, Andrew, Stebbings, Lucy, Hess, Julian M., Rosenberg, Mara, Dunford, Andrew J., Gupta, Manaswi, Imielinski, Marcin, Meyerson, Matthew, Beroukhim, Rameen, Reimand, Juri, Dhingra, Priyanka, Favero, Francesco, Dentro, Stefan, Wintersinger, Jeff, Rudneva, Vasilisa, Park, Ji Wan, Hong, Eun Pyo, Heo, Seong Gu, Kahles, Andre, Soulette, Cameron M., Shiraishi, Yuichi, Liu, Fenglin, He, Yao, Demircioglu, Deniz, Davidson, Natalie R., Greger, Liliana, Li, Siliang, Liu, Dongbing, Stark, Stefan G., Zhang, Fan, Amin, Samirkumar B., Bailey, Peter, Chateigner, Aurelien, Frenkel-Morgenstern, Milana, Hou, Yong, Huska, Matthew R., Kilpinen, Helena, Lamaze, Fabien C., Li, Chang, Li, Xiaobo, Li, Xinyue, Liu, Xingmin, Marin, Maximillian G., Markowski, Julia, Nandi, Tannistha, Ojesina, Akinyemi, I, Pan-Hammarstrom, Qiang, Park, Peter J., Pedamallu, Chandra Sekhar, Su, Hong, Tan, Patrick, Teh, Bin Tean, Wang, Jian, Xiong, Heng, Ye, Chen, Yung, Christina, Zhang, Xiuqing, Zheng, Liangtao, Zhu, Shida, Awadalla, Philip, Creighton, Chad J., Wu, Kui, Yang, Huanming, Goke, Jonathan, Zhang, Zemin, Brooks, Angela N., Martincorena, Inigo, Rubio-Perez, Carlota, Juul, Malene, Schumacher, Steven, Shapira, Ofer, Tamborero, David, Mularoni, Loris, Hornshoj, Henrik, Deu-Pons, Jordi, Muinos, Ferran, Bertl, Johanna, Guo, Qianyun, Bazant, Wojciech, Barrera, Elisabet, Al-Sedairy, Sultan T., Aretz, Axel, Bell, Cindy, Betancourt, Miguel, Buchholz, Christiane, Calvo, Fabien, Chomienne, Christine, Dunn, Michael, Edmonds, Stuart, Green, Eric, Gupta, Shailja, Hutter, Carolyn M., Jegalian, Karine, Jones, Nic, Lu, Youyong, Nakagama, Hitoshi, Nettekoven, Gerd, Planko, Laura, Scott, David, Shibata, Tatsuhiro, Shimizu, Kiyo, Stratton, Michael R., Yugawa, Takashi, Tortora, Giampaolo, VijayRaghavan, K., Zenklusen, Jean C., Knoppers, Bartha M., Aminou, Brice, Bartolome, Javier, Boroevich, Keith A., Boyce, Rich, Buchanan, Alex, Byrne, Niall J., Chen, Zhaohong, Cho, Sunghoon, Choi, Wan, Clapham, Peter, Dow, Michelle T., Dursi, Lewis Jonathan, Eils, Juergen, Farcas, Claudiu, Fayzullaev, Nodirjon, Flicek, Paul, Heath, Allison P., Hofmann, Oliver, Hong, Jongwhi H., Hudson, Thomas J., Huebschmann, Daniel, Ivkovic, Sinisa, Jeon, Seung-Hyup, Jiao, Wei, Kabbe, Rolf, Kerssemakers, Jules N. A., Kim, Hyunghwan, Kim, Jihoon, Koscher, Michael, Koures, Antonios, Kovacevic, Milena, Lawerenz, Chris, Liu, Jia, Mijalkovic, Sanja, Mijalkovic-Lazic, Ana Mijalkovic, Miyano, Satoru, Nastic, Mia, Nicholson, Jonathan, Ocana, David, Ohi, Kazuhiro, Ohno-Machado, Lucila, Pihl, Todd D., Prinz, Manuel, Radovic, Petar, Short, Charles, Sofia, Heidi J., Spring, Jonathan, Struck, Adam J., Tijanic, Nebojsa, Vicente, David, Wang, Zhining, Williams, Ashley, Woo, Youngchoon, Wright, Adam J., Yang, Liming, Hamilton, Mark P., Johnson, Todd A., Kahraman, Abdullah, Kellis, Manolis, Polak, Paz, Sallari, Richard, Sinnott-Armstrong, Nasa, von Mering, Christian, Beltran, Sergi, Gerhard, Daniela S., Gut, Marta, Trotta, Jean-Remi, Whalley, Justin P., Niu, Beifang, Espiritu, Shadrielle M. G., Gao, Shengjie, Huang, Yi, Lalansingh, Christopher M., Teague, Jon W., Wendl, Michael C., Abascal, Federico, Bader, Gary D., Bandopadhayay, Pratiti, Barenboim, Jonathan, Brunak, Soren, Fita, Joana Carlevaro, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Choi, Jung Kyoon, Diamanti, Klev, Fink, J. Lynn, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W., Haradhvala, Nicholas J., Harmanci, Arif O., Helmy, Mohamed, Herrmann, Carl, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Isaev, Keren, Izarzugaza, Jose M. 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S., Long, Georgina, V, Pickett, Hilda A., Pritchard, Antonia L., Pupo, Gulietta M., Saw, Robyn P. M., Schramm, Sarah-Jane, Shang, Catherine A., Shang, Ping, Spillane, Andrew J., Stretch, Jonathan R., Tembe, Varsha, Thompson, John F., Vilain, Ricardo E., Wilmott, James S., Yang, Jean Y., Hayward, Nicholas K., Mann, Graham J., Scolyer, Richard A., Bartlett, John, Bavi, Prashant, Chadwick, Dianne E., Chan-Seng-Yue, Michelle, Cleary, Sean, Connor, Ashton A., Czajka, Karolina, Denroche, Robert E., Dhani, Neesha C., Eagles, Jenna, Gallinger, Steven, Grant, Robert C., Hedley, David, Hollingsworth, Michael A., Jang, Gun Ho, Johns, Jeremy, Kalimuthu, Sangeetha, Liang, Sheng-Ben, Lungu, Ilinca, Luo, Xuemei, Mbabaali, Faridah, McPherson, Treasa A., Miller, Jessica K., Moore, Malcolm J., Notta, Faiyaz, Pasternack, Danielle, Petersen, Gloria M., Roehrl, Michael H. A., Sam, Michelle, Selander, Iris, Serra, Stefano, Shahabi, Sagedeh, Thayer, Sarah P., Timms, Lee E., Wilson, Gavin W., Wilson, Julie M., Wouters, Bradly G., McPherson, John D., Beck, Timothy A., Bhandari, Vinayak, Collins, Colin C., Fleshner, Neil E., Fox, Natalie S., Fraser, Michael, Heisler, Lawrence E., Lalonde, Emilie, Livingstone, Julie, Meng, Alice, Sabelnykova, Veronica Y., Shiah, Yu-Jia, Van Der Kwast, Theodorus, Bristow, Robert G., Ding, Shuai, Fan, Daiming, Li, Lin, Nie, Yongzhan, Xiao, Xiao, Xing, Rui, Yang, Shanlin, Yu, Yingyan, Zhou, Yong, Banks, Rosamonde E., Bourque, Guillaume, Brennan, Paul, Letourneau, Louis, Riazalhosseini, Yasser, Scelo, Ghislaine, Vasudev, Naveen, Viksna, Juris, Lathrop, Mark, Tost, Jorg, Ahn, Sung-Min, Aparicio, Samuel, Arnould, Laurent, Aure, M. R., Bhosle, Shriram G., Birney, Ewan, Borg, Ake, Boyault, Sandrine, Brinkman, Arie B., Brock, Jane E., Broeks, Annegien, Borresen-Dale, Anne-Lise, Caldas, Carlos, Chin, Suet-Feung, Davies, Helen, Desmedt, Christine, Dirix, Luc, Dronov, Serge, Ehinger, Anna, Eyfjord, Jorunn E., Fatima, Aquila, Foekens, John A., Futreal, P. Andrew, Garred, Oystein, Giri, Dilip D., Glodzik, Dominik, Grabau, Dorthe, Hilmarsdottir, Holmfridur, Hooijer, Gerrit K., Jacquemier, Jocelyne, Jang, Se Jin, Jonasson, Jon G., Jonkers, Jos, Kim, Hyung-Yong, King, Tari A., Knappskog, Stian, Kong, Gu, Krishnamurthy, Savitri, Lakhani, Sunil R., Langerod, Anita, Larsimont, Denis, Lee, Hee Jin, Lee, Jeong-Yeon, Lee, Ming Ta Michael, Lingjaerde, Ole Christian, MacGrogan, Gaetan, Martens, John W. M., O'Meara, Sarah, Pauporte, Iris, Pinder, Sarah, Pivot, Xavier, Provenzano, Elena, Purdie, Colin A., Ramakrishna, Manasa, Ramakrishnan, Kamna, Reis-Filho, Jorge, Richardson, Andrea L., Ringner, Markus, Rodriguez, Javier Bartolome, Rodriguez-Gonzalez, F. German, Romieu, Gilles, Salgado, Roberto, Sauer, Torill, Shepherd, Rebecca, Sieuwerts, Anieta M., Simpson, Peter T., Smid, Marcel, Sotiriou, Christos, Span, Paul N., Stefansson, Olafur Andri, Stenhouse, Alasdair, Stunnenberg, Henk G., Sweep, Fred, Tan, Benita Kiat Tee, Thomas, Gilles, Thompson, Alastair M., Tommasi, Stefania, Treilleux, Isabelle, Tutt, Andrew, Ueno, Naoto T., Van Laere, Steven, Van den Eynden, Gert G., Vermeulen, Peter, Viari, Alain, Vincent-Salomon, Anne, Wong, Bernice H., Yates, Lucy, Zou, Xueqing, van Deurzen, Carolien H. M., van de Vijver, Marc J., van't Veer, Laura, Ammerpohl, Ole, Aukema, Sietse, Bergmann, Anke K., Bernhart, Stephan H., Borkhardt, Arndt, Borst, Christoph, Burkhardt, Birgit, Claviez, Alexander, Goebler, Maria Elisabeth, Haake, Andrea, Haas, Siegfried, Hansmann, Martin, Hoell, Jessica, I, Hummel, Michael, Karsch, Dennis, Klapper, Wolfram, Kneba, Michael, Kreuz, Markus, Kube, Dieter, Kueppers, Ralf, Lenze, Dido, Loeffler, Markus, Lopez, Cristina, Mantovani-Loeffler, Luisa, Moeller, Peter, Ott, German, Radlwimmer, Bernhard, Richter, Julia, Rohde, Marius, Rosenstiel, Philip C., Rosenwald, Andreas, Schilhabel, Markus B., Schreiber, Stefan, Stadler, Peter F., Staib, Peter, Stilgenbauer, Stephan, Sungalee, Stephanie, Szczepanowski, Monika, Toprak, Umut H., Truemper, Lorenz H. P., Wagener, Rabea, Zenz, Thorsten, Hovestadt, Volker, von Kalle, Christof, Kool, Marcel, Korshunov, Andrey, Landgraf, Pablo, Lehrach, Hans, Northcott, Paul A., Pfister, Stefan M., Reifenberger, Guido, Warnatz, Hans-Joerg, Wolf, Stephan, Yaspo, Marie-Laure, Assenov, Yassen, Gerhauser, Clarissa, Minner, Sarah, Schlomm, Thorsten, Simon, Ronald, Sauter, Guido, Sueltmann, Holger, Biswas, Nidhan K., Maitra, Arindam, Majumder, Partha P., Sarin, Rajiv, Barbi, Stefano, Bonizzato, Giada, Cantu, Cinzia, Dei Tos, Angelo P., Fassan, Matteo, Grimaldi, Sonia, Luchini, Claudio, Malleo, Giuseppe, Marchegiani, Giovanni, Milella, Michele, Paiella, Salvatore, Pea, Antonio, Pederzoli, Paolo, Ruzzenente, Andrea, Salvia, Roberto, Sperandio, Nicola, Arai, Yasuhito, Hama, Natsuko, Hiraoka, Nobuyoshi, Hosoda, Fumie, Nakamura, Hiromi, Ojima, Hidenori, Okusaka, Takuji, Totoki, Yasushi, Urushidate, Tomoko, Fukayama, Masashi, Ishikawa, Shumpei, Katai, Hitoshi, Katoh, Hiroto, Komura, Daisuke, Rokutan, Hirofumi, Saito-Adachi, Mihoko, Suzuki, Akihiro, Taniguchi, Hirokazu, Tatsuno, Kenji, Ushiku, Tetsuo, Yachida, Shinichi, Yamamoto, Shogo, Aikata, Hiroshi, Arihiro, Koji, Ariizumi, Shun-ichi, Chayama, Kazuaki, Furuta, Mayuko, Gotoh, Kunihito, Hayami, Shinya, Hirano, Satoshi, Kawakami, Yoshiiku, Maejima, Kazuhiro, Nakamura, Toru, Nakano, Kaoru, Ohdan, Hideki, Sasaki-Oku, Aya, Tanaka, Hiroko, Ueno, Masaki, Yamamoto, Masakazu, Yamaue, Hiroki, Choo, Su Pin, Cutcutache, Ioana, Khuntikeo, Narong, Ong, Choon Kiat, Pairojkul, Chawalit, Popescu, Irinel, Ahn, Keun Soo, Aymerich, Marta, Lopez-Guillermo, Armando, Lopez-Otin, Carlos, Puente, Xose S., Campo, Elias, Amary, Fernanda, Baumhoer, Daniel, Behjati, Sam, Bjerkehagen, Bodil, Futreal, P. A., Myklebost, Ola, Pillay, Nischalan, Tarpey, Patrick, Tirabosco, Roberto, Zaikova, Olga, Flanagan, Adrienne M., Boultwood, Jacqueline, Bowen, David T., Cazzola, Mario, Green, Anthony R., Hellstrom-Lindberg, Eva, Malcovati, Luca, Nangalia, Jyoti, Papaemmanuil, Elli, Vyas, Paresh, Ang, Yeng, Barr, Hugh, Beardsmore, Duncan, Eldridge, Matthew, Gossage, James, Grehan, Nicola, Hanna, George B., Hayes, Stephen J., Hupp, Ted R., Khoo, David, Lagergren, Jesper, Lovat, Laurence B., MacRae, Shona, O'Donovan, Maria, O'Neill, J. Robert, Parsons, Simon L., Preston, Shaun R., Puig, Sonia, Roques, Tom, Sanders, Grant, Sothi, Sharmila, Tavare, Simon, Tucker, Olga, Turkington, Richard, Underwood, Timothy J., Welch, Ian, Fitzgerald, Rebecca C., Berney, Daniel M., De Bono, Johann S., Cahill, Declan, Camacho, Niedzica, Dennis, Nening M., Dudderidge, Tim, Edwards, Sandra E., Fisher, Cyril, Foster, Christopher S., Ghori, Mohammed, Gill, Pelvender, Gnanapragasam, Vincent J., Gundem, Gunes, Hamdy, Freddie C., Hawkins, Steve, Hazell, Steven, Howat, William, Isaacs, William B., Karaszi, Katalin, Kay, Jonathan D., Khoo, Vincent, Kote-Jarai, Zsofia, Kremeyer, Barbara, Kumar, Pardeep, Lambert, Adam, Leongamornlert, Daniel A., Livni, Naomi, Lu, Yong-Jie, Luxton, Hayley J., Marsden, Luke, Massie, Charlie E., Matthews, Lucy, Mayer, Erik, McDermott, Ultan, Merson, Sue, Neal, David E., Ng, Anthony, Nicol, David, Ogden, Christopher, Rowe, Edward W., Shah, Nimish C., Thomas, Sarah, Thompson, Alan, Verrill, Clare, Visakorpi, Tapio, Warren, Anne Y., Whitaker, Hayley C., Zhang, Hongwei, van As, Nicholas, Eeles, Rosalind A., Abeshouse, Adam, Agrawal, Nishant, Akbani, Rehan, Al Ahmadie, Hikmat, Albert, Monique, Aldape, Kenneth, Ally, Adrian, Appelbaum, Elizabeth L., Armenia, Joshua, Asa, Sylvia, Auman, J. 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Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).
Published: 2020

8. Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma.

Author: Nobre, Liana, Nobre, Liana, Zapotocky, Michal, Khan, Sara, Fukuoka, Kohei, Fonseca, Adriana, McKeown, Tara, Sumerauer, David, Vicha, Ales, Grajkowska, Wieslawa A, Trubicka, Joanna, Li, Kay Ka Wai, Ng, Ho-Keung, Massimi, Luca, Lee, Ji Yeoun, Kim, Seung-Ki, Zelcer, Shayna, Vasiljevic, Alexandre, Faure-Conter, Cécile, Hauser, Peter, Lach, Boleslaw, van Veelen-Vincent, Marie-Lise, French, Pim J, Van Meir, Erwin G, Weiss, William A, Gupta, Nalin, Pollack, Ian F, Hamilton, Ronald L, Nageswara Rao, Amulya A, Giannini, Caterina, Rubin, Joshua B, Moore, Andrew S, Chambless, Lola B, Vibhakar, Rajeev, Ra, Young Shin, Massimino, Maura, McLendon, Roger E, Wheeler, Helen, Zollo, Massimo, Ferruci, Veronica, Kumabe, Toshihiro, Faria, Claudia C, Sterba, Jaroslav, Jung, Shin, López-Aguilar, Enrique, Mora, Jaume, Carlotti, Carlos G, Olson, James M, Leary, Sarah, Cain, Jason, Krskova, Lenka, Zamecnik, Josef, Hawkins, Cynthia E, Tabori, Uri, Huang, Annie, Bartels, Ute, Northcott, Paul A, Taylor, Michael D, Yip, Stephen, Hansford, Jordan R, Bouffet, Eric, Ramaswamy, Vijay, Nobre, Liana, Nobre, Liana, Zapotocky, Michal, Khan, Sara, Fukuoka, Kohei, Fonseca, Adriana, McKeown, Tara, Sumerauer, David, Vicha, Ales, Grajkowska, Wieslawa A, Trubicka, Joanna, Li, Kay Ka Wai, Ng, Ho-Keung, Massimi, Luca, Lee, Ji Yeoun, Kim, Seung-Ki, Zelcer, Shayna, Vasiljevic, Alexandre, Faure-Conter, Cécile, Hauser, Peter, Lach, Boleslaw, van Veelen-Vincent, Marie-Lise, French, Pim J, Van Meir, Erwin G, Weiss, William A, Gupta, Nalin, Pollack, Ian F, Hamilton, Ronald L, Nageswara Rao, Amulya A, Giannini, Caterina, Rubin, Joshua B, Moore, Andrew S, Chambless, Lola B, Vibhakar, Rajeev, Ra, Young Shin, Massimino, Maura, McLendon, Roger E, Wheeler, Helen, Zollo, Massimo, Ferruci, Veronica, Kumabe, Toshihiro, Faria, Claudia C, Sterba, Jaroslav, Jung, Shin, López-Aguilar, Enrique, Mora, Jaume, Carlotti, Carlos G, Olson, James M, Leary, Sarah, Cain, Jason, Krskova, Lenka, Zamecnik, Josef, Hawkins, Cynthia E, Tabori, Uri, Huang, Annie, Bartels, Ute, Northcott, Paul A, Taylor, Michael D, Yip, Stephen, Hansford, Jordan R, Bouffet, Eric, and Ramaswamy, Vijay
Abstract: Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763-0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses.
Published: 2020

9. Risk-adapted therapy and biological heterogeneity in pineoblastoma: integrated clinico-pathological analysis from the prospective, multi-center SJMB03 and SJYC07 trials.

Author: Liu, Anthony PY, Liu, Anthony PY, Gudenas, Brian, Lin, Tong, Orr, Brent A, Klimo, Paul, Kumar, Rahul, Bouffet, Eric, Gururangan, Sridharan, Crawford, John R, Kellie, Stewart J, Chintagumpala, Murali, Fisher, Michael J, Bowers, Daniel C, Hassall, Tim, Indelicato, Daniel J, Onar-Thomas, Arzu, Ellison, David W, Boop, Frederick A, Merchant, Thomas E, Robinson, Giles W, Northcott, Paul A, Gajjar, Amar, Liu, Anthony PY, Liu, Anthony PY, Gudenas, Brian, Lin, Tong, Orr, Brent A, Klimo, Paul, Kumar, Rahul, Bouffet, Eric, Gururangan, Sridharan, Crawford, John R, Kellie, Stewart J, Chintagumpala, Murali, Fisher, Michael J, Bowers, Daniel C, Hassall, Tim, Indelicato, Daniel J, Onar-Thomas, Arzu, Ellison, David W, Boop, Frederick A, Merchant, Thomas E, Robinson, Giles W, Northcott, Paul A, and Gajjar, Amar
Abstract: Pineoblastoma is a rare embryonal tumor of childhood that is conventionally treated with high-dose craniospinal irradiation (CSI). Multi-dimensional molecular evaluation of pineoblastoma and associated intertumoral heterogeneity is lacking. Herein, we report outcomes and molecular features of children with pineoblastoma from two multi-center, risk-adapted trials (SJMB03 for patients ≥ 3 years; SJYC07 for patients < 3 years) complemented by a non-protocol institutional cohort. The clinical cohort consisted of 58 patients with histologically diagnosed pineoblastoma (SJMB03 = 30, SJYC07 = 12, non-protocol = 16, including 12 managed with SJMB03-like therapy). The SJMB03 protocol comprised risk-adapted CSI (average-risk = 23.4 Gy, high-risk = 36 Gy) with radiation boost to the primary site and adjuvant chemotherapy. The SJYC07 protocol consisted of induction chemotherapy, consolidation with focal radiation (intermediate-risk) or chemotherapy (high-risk), and metronomic maintenance therapy. The molecular cohort comprised 43 pineal parenchymal tumors profiled by DNA methylation array (n = 43), whole-exome sequencing (n = 26), and RNA-sequencing (n = 16). Respective 5-year progression-free survival rates for patients with average-risk or high-risk disease on SJMB03 or SJMB03-like therapy were 100% and 56.5 ± 10.3% (P = 0.007); respective 2-year progression-free survival rates for those with intermediate-risk or high-risk disease on SJYC07 were 14.3 ± 13.2% and 0% (P = 0.375). Of patients with average-risk disease treated with SJMB03/SJMB03-like therapy, 17/18 survived without progression. DNA-methylation analysis revealed four clinically relevant pineoblastoma subgroups: PB-A, PB-B, PB-B-like, and PB-FOXR2. Pineoblastoma subgroups differed in age at diagnosis, propensity for metastasis, cytogenetics, and clinical outcomes. Alterations in the miRNA-processing pathway genes DICER1, DROSHA, and DGCR8 were recurrent and mutually exclusive in PB-B and PB-B
Published: 2020

10. Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma

Author: Nobre, Liana, Zapotocky, Michal, Khan, Sara, Fukuoka, Kohei, Fonseca, Adriana, McKeown, Tara, Sumerauer, David, Vicha, Ales, Grajkowska, Wieslawa A., Trubicka, Joanna, Li, Kay Ka Wai, Ng, Ho Keung, Massimi, Luca, Lee, Ji Yeoun, Kim, Seung Ki, Zelcer, Shayna, Vasiljevic, Alexandre, Faure-Conter, Cécile, Hauser, Peter, Lach, Boleslaw, van Veelen-Vincent, Marie Lise, French, Pim J., Van Meir, Erwin G., Weiss, William A., Gupta, Nalin, Pollack, Ian F., Hamilton, Ronald L., Nageswara Rao, Amulya A., Giannini, Caterina, Rubin, Joshua B., Moore, Andrew S., Chambless, Lola B., Vibhakar, Rajeev, Ra, Young Shin, Massimino, Maura, McLendon, Roger E., Wheeler, Helen, Zollo, Massimo, Ferruci, Veronica, Kumabe, Toshihiro, Faria, Claudia C., Sterba, Jaroslav, Jung, Shin, López-Aguilar, Enrique, Mora, Jaume, Carlotti, Carlos G., Olson, James M., Leary, Sarah, Cain, Jason, Krskova, Lenka, Zamecnik, Josef, Hawkins, Cynthia E., Tabori, Uri, Huang, Annie, Bartels, Ute, Northcott, Paul A., Taylor, Michael D., Yip, Stephen, Hansford, Jordan R., Bouffet, Eric, Ramaswamy, Vijay, Nobre, Liana, Zapotocky, Michal, Khan, Sara, Fukuoka, Kohei, Fonseca, Adriana, McKeown, Tara, Sumerauer, David, Vicha, Ales, Grajkowska, Wieslawa A., Trubicka, Joanna, Li, Kay Ka Wai, Ng, Ho Keung, Massimi, Luca, Lee, Ji Yeoun, Kim, Seung Ki, Zelcer, Shayna, Vasiljevic, Alexandre, Faure-Conter, Cécile, Hauser, Peter, Lach, Boleslaw, van Veelen-Vincent, Marie Lise, French, Pim J., Van Meir, Erwin G., Weiss, William A., Gupta, Nalin, Pollack, Ian F., Hamilton, Ronald L., Nageswara Rao, Amulya A., Giannini, Caterina, Rubin, Joshua B., Moore, Andrew S., Chambless, Lola B., Vibhakar, Rajeev, Ra, Young Shin, Massimino, Maura, McLendon, Roger E., Wheeler, Helen, Zollo, Massimo, Ferruci, Veronica, Kumabe, Toshihiro, Faria, Claudia C., Sterba, Jaroslav, Jung, Shin, López-Aguilar, Enrique, Mora, Jaume, Carlotti, Carlos G., Olson, James M., Leary, Sarah, Cain, Jason, Krskova, Lenka, Zamecnik, Josef, Hawkins, Cynthia E., Tabori, Uri, Huang, Annie, Bartels, Ute, Northcott, Paul A., Taylor, Michael D., Yip, Stephen, Hansford, Jordan R., Bouffet, Eric, and Ramaswamy, Vijay
Abstract: Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.763–0.925) with 15 relapsed individuals identified. Maintenance chemotherapy is identified as a strong predictor of relapse, with individuals receiving high doses of cyclophosphamide or ifosphamide having only one very late molecularly confirmed relapse (p = 0.032). The anatomical location of recurrence is metastatic in 12 of 15 relapses, with 8 of 12 metastatic relapses in the lateral ventricles. Maintenance chemotherapy, specifically cumulative cyclophosphamide doses, is a significant predictor of relapse across WNT MB. Future efforts to de-escalate therapy need to carefully consider not only the radiation dose but also the chemotherapy regimen and the propensity for metastatic relapses.
Published: 2020

11. Pan-cancer analysis of whole genomes

Author: Campbell, Peter J., Getz, Gad, Korbel, Jan O., Stuart, Joshua M., Jennings, Jennifer L., Stein, Lincoln D., Perry, Marc D., Nahal-Bose, Hardeep K., Ouellette, B. F. Francis, Li, Constance H., Rheinbay, Esther, Nielsen, G. Petur, Sgroi, Dennis C., Wu, Chin-Lee, Faquin, William C., Deshpande, Vikram, Boutros, Paul C., Lazar, Alexander J., Hoadley, Katherine A., Louis, David N., Dursi, L. Jonathan, Yung, Christina K., Bailey, Matthew H., Saksena, Gordon, Raine, Keiran M., Buchhalter, Ivo, Kleinheinz, Kortine, Schlesner, Matthias, Zhang, Junjun, Wang, Wenyi, Wheeler, David A., Ding, Li, Simpson, Jared T., O'Connor, Brian D., Yakneen, Sergei, Ellrott, Kyle, Miyoshi, Naoki, Butler, Adam P., Royo, Romina, Shorser, Solomon, I, Vazquez, Miguel, Rausch, Tobias, Tiao, Grace, Waszak, Sebastian M., Rodriguez-Martin, Bernardo, Shringarpure, Suyash, Wu, Dai-Ying, Demidov, German M., Delaneau, Olivier, Hayashi, Shuto, Imoto, Seiya, Habermann, Nina, Segre, Ayellet, V, Garrison, Erik, Cafferkey, Andy, Alvarez, Eva G., Maria Heredia-Genestar, Jose, Muyas, Francesc, Drechsel, Oliver, Bruzos, Alicia L., Temes, Javier, Zamora, Jorge, Baez-Ortega, Adrian, Kim, Hyung-Lae, Mashl, R. Jay, Ye, Kai, DiBiase, Anthony, Huang, Kuan-lin, Letunic, Ivica, McLellan, Michael D., Newhouse, Steven J., Shmaya, Tal, Kumar, Sushant, Wedge, David C., Wright, Mark H., Yellapantula, Venkata D., Gerstein, Mark, Khurana, Ekta, Marques-Bonet, Tomas, Navarro, Arcadi, Bustamante, Carlos D., Siebert, Reiner, Nakagawa, Hidewaki, Easton, Douglas F., Ossowski, Stephan, Tubio, Jose M. C., De La Vega, Francisco M., Estivill, Xavier, Yuen, Denis, Mihaiescu, George L., Omberg, Larsson, Ferretti, Vincent, Sabarinathan, Radhakrishnan, Pich, Oriol, Gonzalez-Perez, Abel, Weiner, Amaro Taylor, Fittall, Matthew W., Demeulemeester, Jonas, Tarabichi, Maxime, Roberts, Nicola D., Van Loo, Peter, Cortes-Ciriano, Isidro, Urban, Lara, Park, Peter, Pitkaenen, Esa, Li, Yilong, Saini, Natalie, Klimczak, Leszek J., Weischenfeldt, Joachim, Sidiropoulos, Nikos, Alexandrov, Ludmil B., Rabionet, Raquel, Escaramis, Georgia, Bosio, Mattia, Holik, Aliaksei Z., Susak, Hana, Prasad, Aparna, Erkek, Serap, Calabrese, Claudia, Raeder, Benjamin, Harrington, Eoghan, Mayes, Simon, Turner, Daniel, Juul, Sissel, Roberts, Steven A., Song, Lei, Koster, Roelof, Mirabello, Lisa, Hua, Xing, Tanskanen, Tomas J., Tojo, Marta, Chen, Jieming, Aaltonen, Lauri A., Ratsch, Gunnar, Schwarz, Roland F., Butte, Atul J., Brazma, Alvis, Chanock, Stephen J., Chatterjee, Nilanjan, Stegle, Oliver, Harismendy, Olivier, Bova, G. Steven, Gordenin, Dmitry A., Haan, David, Sieverling, Lina, Feuerbach, Lars, Chalmers, Don, Joly, Yann, Knoppers, Bartha, Molnar-Gabor, Fruzsina, Phillips, Mark, Thorogood, Adrian, Townend, David, Goldman, Mary, Fonseca, Nuno A., Xiang, Qian, Craft, Brian, Pineiro-Yanez, Elena, Munoz, Alfonso, Petryszak, Robert, Fullgrabe, Anja, Al-Shahrour, Fatima, Keays, Maria, Haussler, David, Weinstein, John, Huber, Wolfgang, Valencia, Alfonso, Papatheodorou, Irene, Zhu, Jingchun, Fan, Yu, Torrents, David, Bieg, Matthias, Chen, Ken, Chong, Zechen, Cibulskis, Kristian, Eils, Roland, Fulton, Robert S., Gelpi, Josep L., Gonzalez, Santiago, Gut, Ivo G., Hach, Faraz, Heinold, Michael, Hu, Taobo, Huang, Vincent, Hutter, Barbara, Jaeger, Natalie, Jung, Jongsun, Kumar, Yogesh, Lalansingh, Christopher, Leshchiner, Ignaty, Livitz, Dimitri, Ma, Eric Z., Maruvka, Yosef E., Milovanovic, Ana, Nielsen, Morten Muhlig, Paramasivam, Nagarajan, Pedersen, Jakob Skou, Puiggros, Montserrat, Sahinalp, S. Cenk, Sarrafi, Iman, Stewart, Chip, Stobbe, Miranda D., Wala, Jeremiah A., Wang, Jiayin, Wendl, Michael, Werner, Johannes, Wu, Zhenggang, Xue, Hong, Yamaguchi, Takafumi N., Yellapantula, Venkata, Davis-Dusenbery, Brandi N., Grossman, Robert L., Kim, Youngwook, Heinold, Michael C., Hinton, Jonathan, Jones, David R., Menzies, Andrew, Stebbings, Lucy, Hess, Julian M., Rosenberg, Mara, Dunford, Andrew J., Gupta, Manaswi, Imielinski, Marcin, Meyerson, Matthew, Beroukhim, Rameen, Reimand, Juri, Dhingra, Priyanka, Favero, Francesco, Dentro, Stefan, Wintersinger, Jeff, Rudneva, Vasilisa, Park, Ji Wan, Hong, Eun Pyo, Heo, Seong Gu, Kahles, Andre, Soulette, Cameron M., Shiraishi, Yuichi, Liu, Fenglin, He, Yao, Demircioglu, Deniz, Davidson, Natalie R., Greger, Liliana, Li, Siliang, Liu, Dongbing, Stark, Stefan G., Zhang, Fan, Amin, Samirkumar B., Bailey, Peter, Chateigner, Aurelien, Frenkel-Morgenstern, Milana, Hou, Yong, Huska, Matthew R., Kilpinen, Helena, Lamaze, Fabien C., Li, Chang, Li, Xiaobo, Li, Xinyue, Liu, Xingmin, Marin, Maximillian G., Markowski, Julia, Nandi, Tannistha, Ojesina, Akinyemi, I, Pan-Hammarstrom, Qiang, Park, Peter J., Pedamallu, Chandra Sekhar, Su, Hong, Tan, Patrick, Teh, Bin Tean, Wang, Jian, Xiong, Heng, Ye, Chen, Yung, Christina, Zhang, Xiuqing, Zheng, Liangtao, Zhu, Shida, Awadalla, Philip, Creighton, Chad J., Wu, Kui, Yang, Huanming, Goke, Jonathan, Zhang, Zemin, Brooks, Angela N., Martincorena, Inigo, Rubio-Perez, Carlota, Juul, Malene, Schumacher, Steven, Shapira, Ofer, Tamborero, David, Mularoni, Loris, Hornshoj, Henrik, Deu-Pons, Jordi, Muinos, Ferran, Bertl, Johanna, Guo, Qianyun, Bazant, Wojciech, Barrera, Elisabet, Al-Sedairy, Sultan T., Aretz, Axel, Bell, Cindy, Betancourt, Miguel, Buchholz, Christiane, Calvo, Fabien, Chomienne, Christine, Dunn, Michael, Edmonds, Stuart, Green, Eric, Gupta, Shailja, Hutter, Carolyn M., Jegalian, Karine, Jones, Nic, Lu, Youyong, Nakagama, Hitoshi, Nettekoven, Gerd, Planko, Laura, Scott, David, Shibata, Tatsuhiro, Shimizu, Kiyo, Stratton, Michael R., Yugawa, Takashi, Tortora, Giampaolo, VijayRaghavan, K., Zenklusen, Jean C., Knoppers, Bartha M., Aminou, Brice, Bartolome, Javier, Boroevich, Keith A., Boyce, Rich, Buchanan, Alex, Byrne, Niall J., Chen, Zhaohong, Cho, Sunghoon, Choi, Wan, Clapham, Peter, Dow, Michelle T., Dursi, Lewis Jonathan, Eils, Juergen, Farcas, Claudiu, Fayzullaev, Nodirjon, Flicek, Paul, Heath, Allison P., Hofmann, Oliver, Hong, Jongwhi H., Hudson, Thomas J., Huebschmann, Daniel, Ivkovic, Sinisa, Jeon, Seung-Hyup, Jiao, Wei, Kabbe, Rolf, Kerssemakers, Jules N. A., Kim, Hyunghwan, Kim, Jihoon, Koscher, Michael, Koures, Antonios, Kovacevic, Milena, Lawerenz, Chris, Liu, Jia, Mijalkovic, Sanja, Mijalkovic-Lazic, Ana Mijalkovic, Miyano, Satoru, Nastic, Mia, Nicholson, Jonathan, Ocana, David, Ohi, Kazuhiro, Ohno-Machado, Lucila, Pihl, Todd D., Prinz, Manuel, Radovic, Petar, Short, Charles, Sofia, Heidi J., Spring, Jonathan, Struck, Adam J., Tijanic, Nebojsa, Vicente, David, Wang, Zhining, Williams, Ashley, Woo, Youngchoon, Wright, Adam J., Yang, Liming, Hamilton, Mark P., Johnson, Todd A., Kahraman, Abdullah, Kellis, Manolis, Polak, Paz, Sallari, Richard, Sinnott-Armstrong, Nasa, von Mering, Christian, Beltran, Sergi, Gerhard, Daniela S., Gut, Marta, Trotta, Jean-Remi, Whalley, Justin P., Niu, Beifang, Espiritu, Shadrielle M. G., Gao, Shengjie, Huang, Yi, Lalansingh, Christopher M., Teague, Jon W., Wendl, Michael C., Abascal, Federico, Bader, Gary D., Bandopadhayay, Pratiti, Barenboim, Jonathan, Brunak, Soren, Fita, Joana Carlevaro, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Choi, Jung Kyoon, Diamanti, Klev, Fink, J. Lynn, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W., Haradhvala, Nicholas J., Harmanci, Arif O., Helmy, Mohamed, Herrmann, Carl, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Isaev, Keren, Izarzugaza, Jose M. G., Johnson, Rory, Juul, Randi Istrup, Kim, Jaegil, Kim, Jong K., Komorowski, Jan, Lanzos, Andres, Larsson, Erik, Lee, Donghoon, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Fundichely, Alexander Martinez, McGillivray, Patrick D., Meyerson, William, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pons, Tirso, Pulido-Tamayo, Sergio, Reyes Salazar, Iker, Reyna, Matthew A., Rubin, Mark A., Salichos, Leonidas, Sander, Chris, Schumacher, Steven E., Shackleton, Mark, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Tsunoda, Tatsuhiko, Umer, Husen M., Uuskula-Reimand, Liis, Verbeke, Lieven P. C., Wadelius, Claes, Wadi, Lina, Warrell, Jonathan, Wu, Guanming, Yu, Jun, Zhang, Jing, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, Lawrence, Michael S., Raphael, Benjamin J., Bailey, Peter J., Craft, David, Goldman, Mary J., Aburatani, Hiroyuki, Binder, Hans, Dinh, Huy Q., Heath, Simon C., Hoffmann, Steve, Imbusch, Charles David, Kretzmer, Helene, Laird, Peter W., Martin-Subero, Jose, I, Nagae, Genta, Shen, Hui, Wang, Qi, Weichenhan, Dieter, Zhou, Wanding, Berman, Benjamin P., Brors, Benedikt, Plass, Christoph, Akdemir, Kadir C., Bowtell, David D. L., Burns, Kathleen H., Busanovich, John, Chan, Kin, Dueso-Barroso, Ana, Edwards, Paul A., Etemadmoghadam, Dariush, Haber, James E., Jones, David T. W., Ju, Young Seok, Kazanov, Marat D., Koh, Youngil, Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Lynch, Andy G., Macintyre, Geoff, Markowetz, Florian, Navarro, Fabio C. P., Pearson, John, V, Rippe, Karsten, Scully, Ralph, Villasante, Izar, Waddell, Nicola, Yang, Lixing, Yao, Xiaotong, Yoon, Sung-Soo, Zhang, Cheng-Zhong, Bergstrom, Erik N., Boot, Arnoud, Covington, Kyle, Fujimoto, Akihiro, Huang, Mi Ni, Islam, S. M. Ashiqul, McPherson, John R., Morganella, Sandro, Mustonen, Ville, Ng, Alvin Wei Tian, Prokopec, Stephenie D., Vazquez-Garcia, Ignacio, Wu, Yang, Yousif, Fouad, Yu, Willie, Rozen, Steven G., Rudneva, Vasilisa A., Shringarpure, Suyash S., Turner, Daniel J., Xia, Tian, Atwal, Gurnit, Chang, David K., Cooke, Susanna L., Faltas, Bishoy M., Haider, Syed, Kaiser, Vera B., Karlic, Rosa, Kato, Mamoru, Kubler, Kirsten, Margolin, Adam, Martin, Sancha, Nik-Zainal, Serena, P'ng, Christine, Semple, Colin A., Smith, Jaclyn, Sun, Ren X., Thai, Kevin, Wright, Derek W., Yuan, Ke, Biankin, Andrew, V, Garraway, Levi, Grimmond, Sean M., Adams, David J., Anur, Pavana, Cao, Shaolong, Christie, Elizabeth L., Cmero, Marek, Cun, Yupeng, Dawson, Kevin J., Dentro, Stefan C., Deshwar, Amit G., Donmez, Nilgun, Drews, Ruben M., Gerstung, Moritz, Ha, Gavin, Haase, Kerstin, Jerman, Lara, Ji, Yuan, Jolly, Clemency, Lee, Juhee, Lee-Six, Henry, Malikic, Salem, Mitchell, Thomas J., Morris, Quaid D., Oesper, Layla, Peifer, Martin, Peto, Myron, Rosebrock, Daniel, Rubanova, Yulia, Salcedo, Adriana, Sengupta, Subhajit, Shi, Ruian, Shin, Seung Jun, Spiro, Oliver, Vembu, Shankar, Wintersinger, Jeffrey A., Yang, Tsun-Po, Yu, Kaixian, Zhu, Hongtu, Spellman, Paul T., Weinstein, John N., Chen, Yiwen, Fujita, Masashi, Han, Leng, Hasegawa, Takanori, Komura, Mitsuhiro, Li, Jun, Mizuno, Shinichi, Shimizu, Eigo, Wang, Yumeng, Xu, Yanxun, Yamaguchi, Rui, Yang, Fan, Yang, Yang, Yoon, Christopher J., Yuan, Yuan, Liang, Han, Alawi, Malik, Borozan, Ivan, Brewer, Daniel S., Cooper, Colin S., Desai, Nikita, Grundhoff, Adam, Iskar, Murat, Su, Xiaoping, Zapatka, Marc, Lichter, Peter, Alsop, Kathryn, Bruxner, Timothy J. C., Christ, Angelika N., Cordner, Stephen M., Cowin, Prue A., Drapkin, Ronny, Fereday, Sian, George, Joshy, Hamilton, Anne, Holmes, Oliver, Hung, Jillian A., Kassahn, Karin S., Kazakoff, Stephen H., Kennedy, Catherine J., Leonard, Conrad R., Mileshkin, Linda, Miller, David K., Arnau, Gisela Mir, Mitchell, Chris, Newell, Felicity, Nones, Katia, Patch, Ann-Marie, Quinn, Michael C., Taylor, Darrin F., Thorne, Heather, Traficante, Nadia, Vedururu, Ravikiran, Waddell, Nick M., Waring, Paul M., Wood, Scott, Xu, Qinying, DeFazio, Anna, Anderson, Matthew J., Antonello, Davide, Barbour, Andrew P., Bassi, Claudio, Bersani, Samantha, Cataldo, Ivana, Chantrill, Lorraine A., Chiew, Yoke-Eng, Chou, Angela, Cingarlini, Sara, Cloonan, Nicole, Corbo, Vincenzo, Davi, Maria Vittoria, Duthie, Fraser R., Gill, Anthony J., Graham, Janet S., Harliwong, Ivon, Jamieson, Nigel B., Johns, Amber L., Kench, James G., Landoni, Luca, Lawlor, Rita T., Mafficini, Andrea, Merrett, Neil D., Miotto, Marco, Musgrove, Elizabeth A., Nagrial, Adnan M., Oien, Karin A., Pajic, Marina, Pinese, Mark, Robertson, Alan J., Rooman, Ilse, Rusev, Borislav C., Samra, Jaswinder S., Scardoni, Maria, Scarlett, Christopher J., Scarpa, Aldo, Sereni, Elisabetta, Sikora, Katarzyna O., Simbolo, Michele, Taschuk, Morgan L., Toon, Christopher W., Vicentini, Caterina, Wu, Jianmin, Zeps, Nikolajs, Behren, Andreas, Burke, Hazel, Cebon, Jonathan, Dagg, Rebecca A., De Paoli-Iseppi, Ricardo, Dutton-Regester, Ken, Field, Matthew A., Fitzgerald, Anna, Hersey, Peter, Jakrot, Valerie, Johansson, Peter A., Kakavand, Hojabr, Kefford, Richard F., Lau, Loretta M. S., Long, Georgina, V, Pickett, Hilda A., Pritchard, Antonia L., Pupo, Gulietta M., Saw, Robyn P. M., Schramm, Sarah-Jane, Shang, Catherine A., Shang, Ping, Spillane, Andrew J., Stretch, Jonathan R., Tembe, Varsha, Thompson, John F., Vilain, Ricardo E., Wilmott, James S., Yang, Jean Y., Hayward, Nicholas K., Mann, Graham J., Scolyer, Richard A., Bartlett, John, Bavi, Prashant, Chadwick, Dianne E., Chan-Seng-Yue, Michelle, Cleary, Sean, Connor, Ashton A., Czajka, Karolina, Denroche, Robert E., Dhani, Neesha C., Eagles, Jenna, Gallinger, Steven, Grant, Robert C., Hedley, David, Hollingsworth, Michael A., Jang, Gun Ho, Johns, Jeremy, Kalimuthu, Sangeetha, Liang, Sheng-Ben, Lungu, Ilinca, Luo, Xuemei, Mbabaali, Faridah, McPherson, Treasa A., Miller, Jessica K., Moore, Malcolm J., Notta, Faiyaz, Pasternack, Danielle, Petersen, Gloria M., Roehrl, Michael H. A., Sam, Michelle, Selander, Iris, Serra, Stefano, Shahabi, Sagedeh, Thayer, Sarah P., Timms, Lee E., Wilson, Gavin W., Wilson, Julie M., Wouters, Bradly G., McPherson, John D., Beck, Timothy A., Bhandari, Vinayak, Collins, Colin C., Fleshner, Neil E., Fox, Natalie S., Fraser, Michael, Heisler, Lawrence E., Lalonde, Emilie, Livingstone, Julie, Meng, Alice, Sabelnykova, Veronica Y., Shiah, Yu-Jia, Van Der Kwast, Theodorus, Bristow, Robert G., Ding, Shuai, Fan, Daiming, Li, Lin, Nie, Yongzhan, Xiao, Xiao, Xing, Rui, Yang, Shanlin, Yu, Yingyan, Zhou, Yong, Banks, Rosamonde E., Bourque, Guillaume, Brennan, Paul, Letourneau, Louis, Riazalhosseini, Yasser, Scelo, Ghislaine, Vasudev, Naveen, Viksna, Juris, Lathrop, Mark, Tost, Jorg, Ahn, Sung-Min, Aparicio, Samuel, Arnould, Laurent, Aure, M. R., Bhosle, Shriram G., Birney, Ewan, Borg, Ake, Boyault, Sandrine, Brinkman, Arie B., Brock, Jane E., Broeks, Annegien, Borresen-Dale, Anne-Lise, Caldas, Carlos, Chin, Suet-Feung, Davies, Helen, Desmedt, Christine, Dirix, Luc, Dronov, Serge, Ehinger, Anna, Eyfjord, Jorunn E., Fatima, Aquila, Foekens, John A., Futreal, P. Andrew, Garred, Oystein, Giri, Dilip D., Glodzik, Dominik, Grabau, Dorthe, Hilmarsdottir, Holmfridur, Hooijer, Gerrit K., Jacquemier, Jocelyne, Jang, Se Jin, Jonasson, Jon G., Jonkers, Jos, Kim, Hyung-Yong, King, Tari A., Knappskog, Stian, Kong, Gu, Krishnamurthy, Savitri, Lakhani, Sunil R., Langerod, Anita, Larsimont, Denis, Lee, Hee Jin, Lee, Jeong-Yeon, Lee, Ming Ta Michael, Lingjaerde, Ole Christian, MacGrogan, Gaetan, Martens, John W. M., O'Meara, Sarah, Pauporte, Iris, Pinder, Sarah, Pivot, Xavier, Provenzano, Elena, Purdie, Colin A., Ramakrishna, Manasa, Ramakrishnan, Kamna, Reis-Filho, Jorge, Richardson, Andrea L., Ringner, Markus, Rodriguez, Javier Bartolome, Rodriguez-Gonzalez, F. German, Romieu, Gilles, Salgado, Roberto, Sauer, Torill, Shepherd, Rebecca, Sieuwerts, Anieta M., Simpson, Peter T., Smid, Marcel, Sotiriou, Christos, Span, Paul N., Stefansson, Olafur Andri, Stenhouse, Alasdair, Stunnenberg, Henk G., Sweep, Fred, Tan, Benita Kiat Tee, Thomas, Gilles, Thompson, Alastair M., Tommasi, Stefania, Treilleux, Isabelle, Tutt, Andrew, Ueno, Naoto T., Van Laere, Steven, Van den Eynden, Gert G., Vermeulen, Peter, Viari, Alain, Vincent-Salomon, Anne, Wong, Bernice H., Yates, Lucy, Zou, Xueqing, van Deurzen, Carolien H. M., van de Vijver, Marc J., van't Veer, Laura, Ammerpohl, Ole, Aukema, Sietse, Bergmann, Anke K., Bernhart, Stephan H., Borkhardt, Arndt, Borst, Christoph, Burkhardt, Birgit, Claviez, Alexander, Goebler, Maria Elisabeth, Haake, Andrea, Haas, Siegfried, Hansmann, Martin, Hoell, Jessica, I, Hummel, Michael, Karsch, Dennis, Klapper, Wolfram, Kneba, Michael, Kreuz, Markus, Kube, Dieter, Kueppers, Ralf, Lenze, Dido, Loeffler, Markus, Lopez, Cristina, Mantovani-Loeffler, Luisa, Moeller, Peter, Ott, German, Radlwimmer, Bernhard, Richter, Julia, Rohde, Marius, Rosenstiel, Philip C., Rosenwald, Andreas, Schilhabel, Markus B., Schreiber, Stefan, Stadler, Peter F., Staib, Peter, Stilgenbauer, Stephan, Sungalee, Stephanie, Szczepanowski, Monika, Toprak, Umut H., Truemper, Lorenz H. P., Wagener, Rabea, Zenz, Thorsten, Hovestadt, Volker, von Kalle, Christof, Kool, Marcel, Korshunov, Andrey, Landgraf, Pablo, Lehrach, Hans, Northcott, Paul A., Pfister, Stefan M., Reifenberger, Guido, Warnatz, Hans-Joerg, Wolf, Stephan, Yaspo, Marie-Laure, Assenov, Yassen, Gerhauser, Clarissa, Minner, Sarah, Schlomm, Thorsten, Simon, Ronald, Sauter, Guido, Sueltmann, Holger, Biswas, Nidhan K., Maitra, Arindam, Majumder, Partha P., Sarin, Rajiv, Barbi, Stefano, Bonizzato, Giada, Cantu, Cinzia, Dei Tos, Angelo P., Fassan, Matteo, Grimaldi, Sonia, Luchini, Claudio, Malleo, Giuseppe, Marchegiani, Giovanni, Milella, Michele, Paiella, Salvatore, Pea, Antonio, Pederzoli, Paolo, Ruzzenente, Andrea, Salvia, Roberto, Sperandio, Nicola, Arai, Yasuhito, Hama, Natsuko, Hiraoka, Nobuyoshi, Hosoda, Fumie, Nakamura, Hiromi, Ojima, Hidenori, Okusaka, Takuji, Totoki, Yasushi, Urushidate, Tomoko, Fukayama, Masashi, Ishikawa, Shumpei, Katai, Hitoshi, Katoh, Hiroto, Komura, Daisuke, Rokutan, Hirofumi, Saito-Adachi, Mihoko, Suzuki, Akihiro, Taniguchi, Hirokazu, Tatsuno, Kenji, Ushiku, Tetsuo, Yachida, Shinichi, Yamamoto, Shogo, Aikata, Hiroshi, Arihiro, Koji, Ariizumi, Shun-ichi, Chayama, Kazuaki, Furuta, Mayuko, Gotoh, Kunihito, Hayami, Shinya, Hirano, Satoshi, Kawakami, Yoshiiku, Maejima, Kazuhiro, Nakamura, Toru, Nakano, Kaoru, Ohdan, Hideki, Sasaki-Oku, Aya, Tanaka, Hiroko, Ueno, Masaki, Yamamoto, Masakazu, Yamaue, Hiroki, Choo, Su Pin, Cutcutache, Ioana, Khuntikeo, Narong, Ong, Choon Kiat, Pairojkul, Chawalit, Popescu, Irinel, Ahn, Keun Soo, Aymerich, Marta, Lopez-Guillermo, Armando, Lopez-Otin, Carlos, Puente, Xose S., Campo, Elias, Amary, Fernanda, Baumhoer, Daniel, Behjati, Sam, Bjerkehagen, Bodil, Futreal, P. A., Myklebost, Ola, Pillay, Nischalan, Tarpey, Patrick, Tirabosco, Roberto, Zaikova, Olga, Flanagan, Adrienne M., Boultwood, Jacqueline, Bowen, David T., Cazzola, Mario, Green, Anthony R., Hellstrom-Lindberg, Eva, Malcovati, Luca, Nangalia, Jyoti, Papaemmanuil, Elli, Vyas, Paresh, Ang, Yeng, Barr, Hugh, Beardsmore, Duncan, Eldridge, Matthew, Gossage, James, Grehan, Nicola, Hanna, George B., Hayes, Stephen J., Hupp, Ted R., Khoo, David, Lagergren, Jesper, Lovat, Laurence B., MacRae, Shona, O'Donovan, Maria, O'Neill, J. Robert, Parsons, Simon L., Preston, Shaun R., Puig, Sonia, Roques, Tom, Sanders, Grant, Sothi, Sharmila, Tavare, Simon, Tucker, Olga, Turkington, Richard, Underwood, Timothy J., Welch, Ian, Fitzgerald, Rebecca C., Berney, Daniel M., De Bono, Johann S., Cahill, Declan, Camacho, Niedzica, Dennis, Nening M., Dudderidge, Tim, Edwards, Sandra E., Fisher, Cyril, Foster, Christopher S., Ghori, Mohammed, Gill, Pelvender, Gnanapragasam, Vincent J., Gundem, Gunes, Hamdy, Freddie C., Hawkins, Steve, Hazell, Steven, Howat, William, Isaacs, William B., Karaszi, Katalin, Kay, Jonathan D., Khoo, Vincent, Kote-Jarai, Zsofia, Kremeyer, Barbara, Kumar, Pardeep, Lambert, Adam, Leongamornlert, Daniel A., Livni, Naomi, Lu, Yong-Jie, Luxton, Hayley J., Marsden, Luke, Massie, Charlie E., Matthews, Lucy, Mayer, Erik, McDermott, Ultan, Merson, Sue, Neal, David E., Ng, Anthony, Nicol, David, Ogden, Christopher, Rowe, Edward W., Shah, Nimish C., Thomas, Sarah, Thompson, Alan, Verrill, Clare, Visakorpi, Tapio, Warren, Anne Y., Whitaker, Hayley C., Zhang, Hongwei, van As, Nicholas, Eeles, Rosalind A., Abeshouse, Adam, Agrawal, Nishant, Akbani, Rehan, Al Ahmadie, Hikmat, Albert, Monique, Aldape, Kenneth, Ally, Adrian, Appelbaum, Elizabeth L., Armenia, Joshua, Asa, Sylvia, Auman, J. Todd, Balasundaram, Miruna, Balu, Saianand, Barnholtz-Sloan, Jill, Bathe, Oliver F., Baylin, Stephen B., Benz, Christopher, Berchuck, Andrew, Berrios, Mario, Bigner, Darell, Birrer, Michael, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S., Bosenberg, Marcus, Bowlby, Reanne, Boyd, Jeffrey, Broaddus, Russell R., Brock, Malcolm, Brooks, Denise, Bullman, Susan, Caesar-Johnson, Samantha J., Carey, Thomas E., Carlsen, Rebecca, Cerfolio, Robert, Chandan, Vishal S., Chen, Hsiao-Wei, Cherniack, Andrew D., Chien, Jeremy, Cho, Juok, Chuah, Eric, Cibulskis, Carrie, Cope, Leslie, Cordes, Matthew G., Curley, Erin, Czerniak, Bogdan, Danilova, Ludmila, Davis, Ian J., Defreitas, Timothy, Demchok, John A., Dhalla, Noreen, Dhir, Rajiv, Doddapaneni, HarshaVardhan, El-Naggar, Adel, Felau, Ina, Ferguson, Martin L., Finocchiaro, Gaetano, Fong, Kwun M., Frazer, Scott, Friedman, William, Fronick, Catrina C., Fulton, Lucinda A., Gabriel, Stacey B., Gao, Jianjiong, Gehlenborg, Nils, Gershenwald, Jeffrey E., Ghossein, Ronald, Giama, Nasra H., Gibbs, Richard A., Gomez, Carmen, Govindan, Ramaswamy, Hayes, D. Neil, Hegde, Apurva M., Heiman, David, I, Heins, Zachary, Hepperla, Austin J., Holbrook, Andrea, Holt, Robert A., Hoyle, Alan P., Hruban, Ralph H., Hu, Jianhong, Huang, Mei, Huntsman, David, Huse, Jason, Donahue, Christine A. Iacobuzio, Ittmann, Michael, Jayaseelan, Joy C., Jefferys, Stuart R., Jones, Corbin D., Jones, Steven J. M., Juhl, Hartmut, Kang, Koo Jeong, Karlan, Beth, Kasaian, Katayoon, Kebebew, Electron, Kim, Hark Kyun, Korchina, Viktoriya, Kundra, Ritika, Lai, Phillip H., Lander, Eric, Le, Xuan, Lee, Darlene, Levine, Douglas A., Lewis, Lora, Ley, Tim, Li, Haiyan Irene, Lin, Pei, Linehan, W. M., Liu, Fei Fei, Lu, Yiling, Lype, Lisa, Ma, Yussanne, Maglinte, Dennis T., Mardis, Elaine R., Marks, Jeffrey, Marra, Marco A., Matthew, Thomas J., Mayo, Michael, McCune, Karen, Meier, Samuel R., Meng, Shaowu, Mieczkowski, Piotr A., Mikkelsen, Tom, Miller, Christopher A., Mills, Gordon B., Moore, Richard A., Morrison, Carl, Mose, Lisle E., Moser, Catherine D., Mungall, Andrew J., Mungall, Karen, Mutch, David, Muzny, Donna M., Myers, Jerome, Newton, Yulia, Noble, Michael S., O'Donnell, Peter, O'Neill, Brian Patrick, Ochoa, Angelica, Park, Joong-Won, Parker, Joel S., Pass, Harvey, Pastore, Alessandro, Pennell, Nathan A., Perou, Charles M., Petrelli, Nicholas, Potapova, Olga, Rader, Janet S., Ramalingam, Suresh, Rathmell, W. Kimryn, Reuter, Victor, Reynolds, Sheila M., Ringel, Matthew, Roach, Jeffrey, Roberts, Lewis R., Robertson, A. Gordon, Sadeghi, Sara, Saller, Charles, Sanchez-Vega, Francisco, Schadendorf, Dirk, Schein, Jacqueline E., Schmidt, Heather K., Schultz, Nikolaus, Seethala, Raja, Senbabaoglu, Yasin, Shelton, Troy, Shi, Yan, Shih, Juliann, Shmulevich, Ilya, Shriver, Craig, Signoretti, Sabina, Simons, Janae, V, Singer, Samuel, Sipahimalani, Payal, Skelly, Tara J., McCune, Karen Smith, Socci, Nicholas D., Soloway, Matthew G., Sood, Anil K., Tam, Angela, Tan, Donghui, Tarnuzzer, Roy, Thiessen, Nina, Thompson, R. Houston, Thorne, Leigh B., Tsao, Ming, Umbricht, Christopher, Van Den Berg, David J., Van Meir, Erwin G., Veluvolu, Umadevi, Voet, Douglas, Wang, Linghua, Weinberger, Paul, Weisenberger, Daniel J., Wigle, Dennis, Wilkerson, Matthew D., Wilson, Richard K., Winterhoff, Boris, Wiznerowicz, Maciej, Wong, Tina, Wong, Winghing, Xi, Liu, Yau, Christina, Zhang, Hailei, Zhang, Hongxin, Zhang, Jiashan, Campbell, Peter J., Getz, Gad, Korbel, Jan O., Stuart, Joshua M., Jennings, Jennifer L., Stein, Lincoln D., Perry, Marc D., Nahal-Bose, Hardeep K., Ouellette, B. F. Francis, Li, Constance H., Rheinbay, Esther, Nielsen, G. Petur, Sgroi, Dennis C., Wu, Chin-Lee, Faquin, William C., Deshpande, Vikram, Boutros, Paul C., Lazar, Alexander J., Hoadley, Katherine A., Louis, David N., Dursi, L. Jonathan, Yung, Christina K., Bailey, Matthew H., Saksena, Gordon, Raine, Keiran M., Buchhalter, Ivo, Kleinheinz, Kortine, Schlesner, Matthias, Zhang, Junjun, Wang, Wenyi, Wheeler, David A., Ding, Li, Simpson, Jared T., O'Connor, Brian D., Yakneen, Sergei, Ellrott, Kyle, Miyoshi, Naoki, Butler, Adam P., Royo, Romina, Shorser, Solomon, I, Vazquez, Miguel, Rausch, Tobias, Tiao, Grace, Waszak, Sebastian M., Rodriguez-Martin, Bernardo, Shringarpure, Suyash, Wu, Dai-Ying, Demidov, German M., Delaneau, Olivier, Hayashi, Shuto, Imoto, Seiya, Habermann, Nina, Segre, Ayellet, V, Garrison, Erik, Cafferkey, Andy, Alvarez, Eva G., Maria Heredia-Genestar, Jose, Muyas, Francesc, Drechsel, Oliver, Bruzos, Alicia L., Temes, Javier, Zamora, Jorge, Baez-Ortega, Adrian, Kim, Hyung-Lae, Mashl, R. Jay, Ye, Kai, DiBiase, Anthony, Huang, Kuan-lin, Letunic, Ivica, McLellan, Michael D., Newhouse, Steven J., Shmaya, Tal, Kumar, Sushant, Wedge, David C., Wright, Mark H., Yellapantula, Venkata D., Gerstein, Mark, Khurana, Ekta, Marques-Bonet, Tomas, Navarro, Arcadi, Bustamante, Carlos D., Siebert, Reiner, Nakagawa, Hidewaki, Easton, Douglas F., Ossowski, Stephan, Tubio, Jose M. C., De La Vega, Francisco M., Estivill, Xavier, Yuen, Denis, Mihaiescu, George L., Omberg, Larsson, Ferretti, Vincent, Sabarinathan, Radhakrishnan, Pich, Oriol, Gonzalez-Perez, Abel, Weiner, Amaro Taylor, Fittall, Matthew W., Demeulemeester, Jonas, Tarabichi, Maxime, Roberts, Nicola D., Van Loo, Peter, Cortes-Ciriano, Isidro, Urban, Lara, Park, Peter, Pitkaenen, Esa, Li, Yilong, Saini, Natalie, Klimczak, Leszek J., Weischenfeldt, Joachim, Sidiropoulos, Nikos, Alexandrov, Ludmil B., Rabionet, Raquel, Escaramis, Georgia, Bosio, Mattia, Holik, Aliaksei Z., Susak, Hana, Prasad, Aparna, Erkek, Serap, Calabrese, Claudia, Raeder, Benjamin, Harrington, Eoghan, Mayes, Simon, Turner, Daniel, Juul, Sissel, Roberts, Steven A., Song, Lei, Koster, Roelof, Mirabello, Lisa, Hua, Xing, Tanskanen, Tomas J., Tojo, Marta, Chen, Jieming, Aaltonen, Lauri A., Ratsch, Gunnar, Schwarz, Roland F., Butte, Atul J., Brazma, Alvis, Chanock, Stephen J., Chatterjee, Nilanjan, Stegle, Oliver, Harismendy, Olivier, Bova, G. Steven, Gordenin, Dmitry A., Haan, David, Sieverling, Lina, Feuerbach, Lars, Chalmers, Don, Joly, Yann, Knoppers, Bartha, Molnar-Gabor, Fruzsina, Phillips, Mark, Thorogood, Adrian, Townend, David, Goldman, Mary, Fonseca, Nuno A., Xiang, Qian, Craft, Brian, Pineiro-Yanez, Elena, Munoz, Alfonso, Petryszak, Robert, Fullgrabe, Anja, Al-Shahrour, Fatima, Keays, Maria, Haussler, David, Weinstein, John, Huber, Wolfgang, Valencia, Alfonso, Papatheodorou, Irene, Zhu, Jingchun, Fan, Yu, Torrents, David, Bieg, Matthias, Chen, Ken, Chong, Zechen, Cibulskis, Kristian, Eils, Roland, Fulton, Robert S., Gelpi, Josep L., Gonzalez, Santiago, Gut, Ivo G., Hach, Faraz, Heinold, Michael, Hu, Taobo, Huang, Vincent, Hutter, Barbara, Jaeger, Natalie, Jung, Jongsun, Kumar, Yogesh, Lalansingh, Christopher, Leshchiner, Ignaty, Livitz, Dimitri, Ma, Eric Z., Maruvka, Yosef E., Milovanovic, Ana, Nielsen, Morten Muhlig, Paramasivam, Nagarajan, Pedersen, Jakob Skou, Puiggros, Montserrat, Sahinalp, S. Cenk, Sarrafi, Iman, Stewart, Chip, Stobbe, Miranda D., Wala, Jeremiah A., Wang, Jiayin, Wendl, Michael, Werner, Johannes, Wu, Zhenggang, Xue, Hong, Yamaguchi, Takafumi N., Yellapantula, Venkata, Davis-Dusenbery, Brandi N., Grossman, Robert L., Kim, Youngwook, Heinold, Michael C., Hinton, Jonathan, Jones, David R., Menzies, Andrew, Stebbings, Lucy, Hess, Julian M., Rosenberg, Mara, Dunford, Andrew J., Gupta, Manaswi, Imielinski, Marcin, Meyerson, Matthew, Beroukhim, Rameen, Reimand, Juri, Dhingra, Priyanka, Favero, Francesco, Dentro, Stefan, Wintersinger, Jeff, Rudneva, Vasilisa, Park, Ji Wan, Hong, Eun Pyo, Heo, Seong Gu, Kahles, Andre, Soulette, Cameron M., Shiraishi, Yuichi, Liu, Fenglin, He, Yao, Demircioglu, Deniz, Davidson, Natalie R., Greger, Liliana, Li, Siliang, Liu, Dongbing, Stark, Stefan G., Zhang, Fan, Amin, Samirkumar B., Bailey, Peter, Chateigner, Aurelien, Frenkel-Morgenstern, Milana, Hou, Yong, Huska, Matthew R., Kilpinen, Helena, Lamaze, Fabien C., Li, Chang, Li, Xiaobo, Li, Xinyue, Liu, Xingmin, Marin, Maximillian G., Markowski, Julia, Nandi, Tannistha, Ojesina, Akinyemi, I, Pan-Hammarstrom, Qiang, Park, Peter J., Pedamallu, Chandra Sekhar, Su, Hong, Tan, Patrick, Teh, Bin Tean, Wang, Jian, Xiong, Heng, Ye, Chen, Yung, Christina, Zhang, Xiuqing, Zheng, Liangtao, Zhu, Shida, Awadalla, Philip, Creighton, Chad J., Wu, Kui, Yang, Huanming, Goke, Jonathan, Zhang, Zemin, Brooks, Angela N., Martincorena, Inigo, Rubio-Perez, Carlota, Juul, Malene, Schumacher, Steven, Shapira, Ofer, Tamborero, David, Mularoni, Loris, Hornshoj, Henrik, Deu-Pons, Jordi, Muinos, Ferran, Bertl, Johanna, Guo, Qianyun, Bazant, Wojciech, Barrera, Elisabet, Al-Sedairy, Sultan T., Aretz, Axel, Bell, Cindy, Betancourt, Miguel, Buchholz, Christiane, Calvo, Fabien, Chomienne, Christine, Dunn, Michael, Edmonds, Stuart, Green, Eric, Gupta, Shailja, Hutter, Carolyn M., Jegalian, Karine, Jones, Nic, Lu, Youyong, Nakagama, Hitoshi, Nettekoven, Gerd, Planko, Laura, Scott, David, Shibata, Tatsuhiro, Shimizu, Kiyo, Stratton, Michael R., Yugawa, Takashi, Tortora, Giampaolo, VijayRaghavan, K., Zenklusen, Jean C., Knoppers, Bartha M., Aminou, Brice, Bartolome, Javier, Boroevich, Keith A., Boyce, Rich, Buchanan, Alex, Byrne, Niall J., Chen, Zhaohong, Cho, Sunghoon, Choi, Wan, Clapham, Peter, Dow, Michelle T., Dursi, Lewis Jonathan, Eils, Juergen, Farcas, Claudiu, Fayzullaev, Nodirjon, Flicek, Paul, Heath, Allison P., Hofmann, Oliver, Hong, Jongwhi H., Hudson, Thomas J., Huebschmann, Daniel, Ivkovic, Sinisa, Jeon, Seung-Hyup, Jiao, Wei, Kabbe, Rolf, Kerssemakers, Jules N. A., Kim, Hyunghwan, Kim, Jihoon, Koscher, Michael, Koures, Antonios, Kovacevic, Milena, Lawerenz, Chris, Liu, Jia, Mijalkovic, Sanja, Mijalkovic-Lazic, Ana Mijalkovic, Miyano, Satoru, Nastic, Mia, Nicholson, Jonathan, Ocana, David, Ohi, Kazuhiro, Ohno-Machado, Lucila, Pihl, Todd D., Prinz, Manuel, Radovic, Petar, Short, Charles, Sofia, Heidi J., Spring, Jonathan, Struck, Adam J., Tijanic, Nebojsa, Vicente, David, Wang, Zhining, Williams, Ashley, Woo, Youngchoon, Wright, Adam J., Yang, Liming, Hamilton, Mark P., Johnson, Todd A., Kahraman, Abdullah, Kellis, Manolis, Polak, Paz, Sallari, Richard, Sinnott-Armstrong, Nasa, von Mering, Christian, Beltran, Sergi, Gerhard, Daniela S., Gut, Marta, Trotta, Jean-Remi, Whalley, Justin P., Niu, Beifang, Espiritu, Shadrielle M. G., Gao, Shengjie, Huang, Yi, Lalansingh, Christopher M., Teague, Jon W., Wendl, Michael C., Abascal, Federico, Bader, Gary D., Bandopadhayay, Pratiti, Barenboim, Jonathan, Brunak, Soren, Fita, Joana Carlevaro, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Choi, Jung Kyoon, Diamanti, Klev, Fink, J. Lynn, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W., Haradhvala, Nicholas J., Harmanci, Arif O., Helmy, Mohamed, Herrmann, Carl, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Isaev, Keren, Izarzugaza, Jose M. G., Johnson, Rory, Juul, Randi Istrup, Kim, Jaegil, Kim, Jong K., Komorowski, Jan, Lanzos, Andres, Larsson, Erik, Lee, Donghoon, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Fundichely, Alexander Martinez, McGillivray, Patrick D., Meyerson, William, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pons, Tirso, Pulido-Tamayo, Sergio, Reyes Salazar, Iker, Reyna, Matthew A., Rubin, Mark A., Salichos, Leonidas, Sander, Chris, Schumacher, Steven E., Shackleton, Mark, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Tsunoda, Tatsuhiko, Umer, Husen M., Uuskula-Reimand, Liis, Verbeke, Lieven P. C., Wadelius, Claes, Wadi, Lina, Warrell, Jonathan, Wu, Guanming, Yu, Jun, Zhang, Jing, Zhang, Xuanping, Zhang, Yan, Zhao, Zhongming, Zou, Lihua, Lawrence, Michael S., Raphael, Benjamin J., Bailey, Peter J., Craft, David, Goldman, Mary J., Aburatani, Hiroyuki, Binder, Hans, Dinh, Huy Q., Heath, Simon C., Hoffmann, Steve, Imbusch, Charles David, Kretzmer, Helene, Laird, Peter W., Martin-Subero, Jose, I, Nagae, Genta, Shen, Hui, Wang, Qi, Weichenhan, Dieter, Zhou, Wanding, Berman, Benjamin P., Brors, Benedikt, Plass, Christoph, Akdemir, Kadir C., Bowtell, David D. L., Burns, Kathleen H., Busanovich, John, Chan, Kin, Dueso-Barroso, Ana, Edwards, Paul A., Etemadmoghadam, Dariush, Haber, James E., Jones, David T. W., Ju, Young Seok, Kazanov, Marat D., Koh, Youngil, Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Lynch, Andy G., Macintyre, Geoff, Markowetz, Florian, Navarro, Fabio C. P., Pearson, John, V, Rippe, Karsten, Scully, Ralph, Villasante, Izar, Waddell, Nicola, Yang, Lixing, Yao, Xiaotong, Yoon, Sung-Soo, Zhang, Cheng-Zhong, Bergstrom, Erik N., Boot, Arnoud, Covington, Kyle, Fujimoto, Akihiro, Huang, Mi Ni, Islam, S. M. Ashiqul, McPherson, John R., Morganella, Sandro, Mustonen, Ville, Ng, Alvin Wei Tian, Prokopec, Stephenie D., Vazquez-Garcia, Ignacio, Wu, Yang, Yousif, Fouad, Yu, Willie, Rozen, Steven G., Rudneva, Vasilisa A., Shringarpure, Suyash S., Turner, Daniel J., Xia, Tian, Atwal, Gurnit, Chang, David K., Cooke, Susanna L., Faltas, Bishoy M., Haider, Syed, Kaiser, Vera B., Karlic, Rosa, Kato, Mamoru, Kubler, Kirsten, Margolin, Adam, Martin, Sancha, Nik-Zainal, Serena, P'ng, Christine, Semple, Colin A., Smith, Jaclyn, Sun, Ren X., Thai, Kevin, Wright, Derek W., Yuan, Ke, Biankin, Andrew, V, Garraway, Levi, Grimmond, Sean M., Adams, David J., Anur, Pavana, Cao, Shaolong, Christie, Elizabeth L., Cmero, Marek, Cun, Yupeng, Dawson, Kevin J., Dentro, Stefan C., Deshwar, Amit G., Donmez, Nilgun, Drews, Ruben M., Gerstung, Moritz, Ha, Gavin, Haase, Kerstin, Jerman, Lara, Ji, Yuan, Jolly, Clemency, Lee, Juhee, Lee-Six, Henry, Malikic, Salem, Mitchell, Thomas J., Morris, Quaid D., Oesper, Layla, Peifer, Martin, Peto, Myron, Rosebrock, Daniel, Rubanova, Yulia, Salcedo, Adriana, Sengupta, Subhajit, Shi, Ruian, Shin, Seung Jun, Spiro, Oliver, Vembu, Shankar, Wintersinger, Jeffrey A., Yang, Tsun-Po, Yu, Kaixian, Zhu, Hongtu, Spellman, Paul T., Weinstein, John N., Chen, Yiwen, Fujita, Masashi, Han, Leng, Hasegawa, Takanori, Komura, Mitsuhiro, Li, Jun, Mizuno, Shinichi, Shimizu, Eigo, Wang, Yumeng, Xu, Yanxun, Yamaguchi, Rui, Yang, Fan, Yang, Yang, Yoon, Christopher J., Yuan, Yuan, Liang, Han, Alawi, Malik, Borozan, Ivan, Brewer, Daniel S., Cooper, Colin S., Desai, Nikita, Grundhoff, Adam, Iskar, Murat, Su, Xiaoping, Zapatka, Marc, Lichter, Peter, Alsop, Kathryn, Bruxner, Timothy J. C., Christ, Angelika N., Cordner, Stephen M., Cowin, Prue A., Drapkin, Ronny, Fereday, Sian, George, Joshy, Hamilton, Anne, Holmes, Oliver, Hung, Jillian A., Kassahn, Karin S., Kazakoff, Stephen H., Kennedy, Catherine J., Leonard, Conrad R., Mileshkin, Linda, Miller, David K., Arnau, Gisela Mir, Mitchell, Chris, Newell, Felicity, Nones, Katia, Patch, Ann-Marie, Quinn, Michael C., Taylor, Darrin F., Thorne, Heather, Traficante, Nadia, Vedururu, Ravikiran, Waddell, Nick M., Waring, Paul M., Wood, Scott, Xu, Qinying, DeFazio, Anna, Anderson, Matthew J., Antonello, Davide, Barbour, Andrew P., Bassi, Claudio, Bersani, Samantha, Cataldo, Ivana, Chantrill, Lorraine A., Chiew, Yoke-Eng, Chou, Angela, Cingarlini, Sara, Cloonan, Nicole, Corbo, Vincenzo, Davi, Maria Vittoria, Duthie, Fraser R., Gill, Anthony J., Graham, Janet S., Harliwong, Ivon, Jamieson, Nigel B., Johns, Amber L., Kench, James G., Landoni, Luca, Lawlor, Rita T., Mafficini, Andrea, Merrett, Neil D., Miotto, Marco, Musgrove, Elizabeth A., Nagrial, Adnan M., Oien, Karin A., Pajic, Marina, Pinese, Mark, Robertson, Alan J., Rooman, Ilse, Rusev, Borislav C., Samra, Jaswinder S., Scardoni, Maria, Scarlett, Christopher J., Scarpa, Aldo, Sereni, Elisabetta, Sikora, Katarzyna O., Simbolo, Michele, Taschuk, Morgan L., Toon, Christopher W., Vicentini, Caterina, Wu, Jianmin, Zeps, Nikolajs, Behren, Andreas, Burke, Hazel, Cebon, Jonathan, Dagg, Rebecca A., De Paoli-Iseppi, Ricardo, Dutton-Regester, Ken, Field, Matthew A., Fitzgerald, Anna, Hersey, Peter, Jakrot, Valerie, Johansson, Peter A., Kakavand, Hojabr, Kefford, Richard F., Lau, Loretta M. S., Long, Georgina, V, Pickett, Hilda A., Pritchard, Antonia L., Pupo, Gulietta M., Saw, Robyn P. M., Schramm, Sarah-Jane, Shang, Catherine A., Shang, Ping, Spillane, Andrew J., Stretch, Jonathan R., Tembe, Varsha, Thompson, John F., Vilain, Ricardo E., Wilmott, James S., Yang, Jean Y., Hayward, Nicholas K., Mann, Graham J., Scolyer, Richard A., Bartlett, John, Bavi, Prashant, Chadwick, Dianne E., Chan-Seng-Yue, Michelle, Cleary, Sean, Connor, Ashton A., Czajka, Karolina, Denroche, Robert E., Dhani, Neesha C., Eagles, Jenna, Gallinger, Steven, Grant, Robert C., Hedley, David, Hollingsworth, Michael A., Jang, Gun Ho, Johns, Jeremy, Kalimuthu, Sangeetha, Liang, Sheng-Ben, Lungu, Ilinca, Luo, Xuemei, Mbabaali, Faridah, McPherson, Treasa A., Miller, Jessica K., Moore, Malcolm J., Notta, Faiyaz, Pasternack, Danielle, Petersen, Gloria M., Roehrl, Michael H. A., Sam, Michelle, Selander, Iris, Serra, Stefano, Shahabi, Sagedeh, Thayer, Sarah P., Timms, Lee E., Wilson, Gavin W., Wilson, Julie M., Wouters, Bradly G., McPherson, John D., Beck, Timothy A., Bhandari, Vinayak, Collins, Colin C., Fleshner, Neil E., Fox, Natalie S., Fraser, Michael, Heisler, Lawrence E., Lalonde, Emilie, Livingstone, Julie, Meng, Alice, Sabelnykova, Veronica Y., Shiah, Yu-Jia, Van Der Kwast, Theodorus, Bristow, Robert G., Ding, Shuai, Fan, Daiming, Li, Lin, Nie, Yongzhan, Xiao, Xiao, Xing, Rui, Yang, Shanlin, Yu, Yingyan, Zhou, Yong, Banks, Rosamonde E., Bourque, Guillaume, Brennan, Paul, Letourneau, Louis, Riazalhosseini, Yasser, Scelo, Ghislaine, Vasudev, Naveen, Viksna, Juris, Lathrop, Mark, Tost, Jorg, Ahn, Sung-Min, Aparicio, Samuel, Arnould, Laurent, Aure, M. R., Bhosle, Shriram G., Birney, Ewan, Borg, Ake, Boyault, Sandrine, Brinkman, Arie B., Brock, Jane E., Broeks, Annegien, Borresen-Dale, Anne-Lise, Caldas, Carlos, Chin, Suet-Feung, Davies, Helen, Desmedt, Christine, Dirix, Luc, Dronov, Serge, Ehinger, Anna, Eyfjord, Jorunn E., Fatima, Aquila, Foekens, John A., Futreal, P. Andrew, Garred, Oystein, Giri, Dilip D., Glodzik, Dominik, Grabau, Dorthe, Hilmarsdottir, Holmfridur, Hooijer, Gerrit K., Jacquemier, Jocelyne, Jang, Se Jin, Jonasson, Jon G., Jonkers, Jos, Kim, Hyung-Yong, King, Tari A., Knappskog, Stian, Kong, Gu, Krishnamurthy, Savitri, Lakhani, Sunil R., Langerod, Anita, Larsimont, Denis, Lee, Hee Jin, Lee, Jeong-Yeon, Lee, Ming Ta Michael, Lingjaerde, Ole Christian, MacGrogan, Gaetan, Martens, John W. M., O'Meara, Sarah, Pauporte, Iris, Pinder, Sarah, Pivot, Xavier, Provenzano, Elena, Purdie, Colin A., Ramakrishna, Manasa, Ramakrishnan, Kamna, Reis-Filho, Jorge, Richardson, Andrea L., Ringner, Markus, Rodriguez, Javier Bartolome, Rodriguez-Gonzalez, F. German, Romieu, Gilles, Salgado, Roberto, Sauer, Torill, Shepherd, Rebecca, Sieuwerts, Anieta M., Simpson, Peter T., Smid, Marcel, Sotiriou, Christos, Span, Paul N., Stefansson, Olafur Andri, Stenhouse, Alasdair, Stunnenberg, Henk G., Sweep, Fred, Tan, Benita Kiat Tee, Thomas, Gilles, Thompson, Alastair M., Tommasi, Stefania, Treilleux, Isabelle, Tutt, Andrew, Ueno, Naoto T., Van Laere, Steven, Van den Eynden, Gert G., Vermeulen, Peter, Viari, Alain, Vincent-Salomon, Anne, Wong, Bernice H., Yates, Lucy, Zou, Xueqing, van Deurzen, Carolien H. M., van de Vijver, Marc J., van't Veer, Laura, Ammerpohl, Ole, Aukema, Sietse, Bergmann, Anke K., Bernhart, Stephan H., Borkhardt, Arndt, Borst, Christoph, Burkhardt, Birgit, Claviez, Alexander, Goebler, Maria Elisabeth, Haake, Andrea, Haas, Siegfried, Hansmann, Martin, Hoell, Jessica, I, Hummel, Michael, Karsch, Dennis, Klapper, Wolfram, Kneba, Michael, Kreuz, Markus, Kube, Dieter, Kueppers, Ralf, Lenze, Dido, Loeffler, Markus, Lopez, Cristina, Mantovani-Loeffler, Luisa, Moeller, Peter, Ott, German, Radlwimmer, Bernhard, Richter, Julia, Rohde, Marius, Rosenstiel, Philip C., Rosenwald, Andreas, Schilhabel, Markus B., Schreiber, Stefan, Stadler, Peter F., Staib, Peter, Stilgenbauer, Stephan, Sungalee, Stephanie, Szczepanowski, Monika, Toprak, Umut H., Truemper, Lorenz H. P., Wagener, Rabea, Zenz, Thorsten, Hovestadt, Volker, von Kalle, Christof, Kool, Marcel, Korshunov, Andrey, Landgraf, Pablo, Lehrach, Hans, Northcott, Paul A., Pfister, Stefan M., Reifenberger, Guido, Warnatz, Hans-Joerg, Wolf, Stephan, Yaspo, Marie-Laure, Assenov, Yassen, Gerhauser, Clarissa, Minner, Sarah, Schlomm, Thorsten, Simon, Ronald, Sauter, Guido, Sueltmann, Holger, Biswas, Nidhan K., Maitra, Arindam, Majumder, Partha P., Sarin, Rajiv, Barbi, Stefano, Bonizzato, Giada, Cantu, Cinzia, Dei Tos, Angelo P., Fassan, Matteo, Grimaldi, Sonia, Luchini, Claudio, Malleo, Giuseppe, Marchegiani, Giovanni, Milella, Michele, Paiella, Salvatore, Pea, Antonio, Pederzoli, Paolo, Ruzzenente, Andrea, Salvia, Roberto, Sperandio, Nicola, Arai, Yasuhito, Hama, Natsuko, Hiraoka, Nobuyoshi, Hosoda, Fumie, Nakamura, Hiromi, Ojima, Hidenori, Okusaka, Takuji, Totoki, Yasushi, Urushidate, Tomoko, Fukayama, Masashi, Ishikawa, Shumpei, Katai, Hitoshi, Katoh, Hiroto, Komura, Daisuke, Rokutan, Hirofumi, Saito-Adachi, Mihoko, Suzuki, Akihiro, Taniguchi, Hirokazu, Tatsuno, Kenji, Ushiku, Tetsuo, Yachida, Shinichi, Yamamoto, Shogo, Aikata, Hiroshi, Arihiro, Koji, Ariizumi, Shun-ichi, Chayama, Kazuaki, Furuta, Mayuko, Gotoh, Kunihito, Hayami, Shinya, Hirano, Satoshi, Kawakami, Yoshiiku, Maejima, Kazuhiro, Nakamura, Toru, Nakano, Kaoru, Ohdan, Hideki, Sasaki-Oku, Aya, Tanaka, Hiroko, Ueno, Masaki, Yamamoto, Masakazu, Yamaue, Hiroki, Choo, Su Pin, Cutcutache, Ioana, Khuntikeo, Narong, Ong, Choon Kiat, Pairojkul, Chawalit, Popescu, Irinel, Ahn, Keun Soo, Aymerich, Marta, Lopez-Guillermo, Armando, Lopez-Otin, Carlos, Puente, Xose S., Campo, Elias, Amary, Fernanda, Baumhoer, Daniel, Behjati, Sam, Bjerkehagen, Bodil, Futreal, P. A., Myklebost, Ola, Pillay, Nischalan, Tarpey, Patrick, Tirabosco, Roberto, Zaikova, Olga, Flanagan, Adrienne M., Boultwood, Jacqueline, Bowen, David T., Cazzola, Mario, Green, Anthony R., Hellstrom-Lindberg, Eva, Malcovati, Luca, Nangalia, Jyoti, Papaemmanuil, Elli, Vyas, Paresh, Ang, Yeng, Barr, Hugh, Beardsmore, Duncan, Eldridge, Matthew, Gossage, James, Grehan, Nicola, Hanna, George B., Hayes, Stephen J., Hupp, Ted R., Khoo, David, Lagergren, Jesper, Lovat, Laurence B., MacRae, Shona, O'Donovan, Maria, O'Neill, J. Robert, Parsons, Simon L., Preston, Shaun R., Puig, Sonia, Roques, Tom, Sanders, Grant, Sothi, Sharmila, Tavare, Simon, Tucker, Olga, Turkington, Richard, Underwood, Timothy J., Welch, Ian, Fitzgerald, Rebecca C., Berney, Daniel M., De Bono, Johann S., Cahill, Declan, Camacho, Niedzica, Dennis, Nening M., Dudderidge, Tim, Edwards, Sandra E., Fisher, Cyril, Foster, Christopher S., Ghori, Mohammed, Gill, Pelvender, Gnanapragasam, Vincent J., Gundem, Gunes, Hamdy, Freddie C., Hawkins, Steve, Hazell, Steven, Howat, William, Isaacs, William B., Karaszi, Katalin, Kay, Jonathan D., Khoo, Vincent, Kote-Jarai, Zsofia, Kremeyer, Barbara, Kumar, Pardeep, Lambert, Adam, Leongamornlert, Daniel A., Livni, Naomi, Lu, Yong-Jie, Luxton, Hayley J., Marsden, Luke, Massie, Charlie E., Matthews, Lucy, Mayer, Erik, McDermott, Ultan, Merson, Sue, Neal, David E., Ng, Anthony, Nicol, David, Ogden, Christopher, Rowe, Edward W., Shah, Nimish C., Thomas, Sarah, Thompson, Alan, Verrill, Clare, Visakorpi, Tapio, Warren, Anne Y., Whitaker, Hayley C., Zhang, Hongwei, van As, Nicholas, Eeles, Rosalind A., Abeshouse, Adam, Agrawal, Nishant, Akbani, Rehan, Al Ahmadie, Hikmat, Albert, Monique, Aldape, Kenneth, Ally, Adrian, Appelbaum, Elizabeth L., Armenia, Joshua, Asa, Sylvia, Auman, J. Todd, Balasundaram, Miruna, Balu, Saianand, Barnholtz-Sloan, Jill, Bathe, Oliver F., Baylin, Stephen B., Benz, Christopher, Berchuck, Andrew, Berrios, Mario, Bigner, Darell, Birrer, Michael, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S., Bosenberg, Marcus, Bowlby, Reanne, Boyd, Jeffrey, Broaddus, Russell R., Brock, Malcolm, Brooks, Denise, Bullman, Susan, Caesar-Johnson, Samantha J., Carey, Thomas E., Carlsen, Rebecca, Cerfolio, Robert, Chandan, Vishal S., Chen, Hsiao-Wei, Cherniack, Andrew D., Chien, Jeremy, Cho, Juok, Chuah, Eric, Cibulskis, Carrie, Cope, Leslie, Cordes, Matthew G., Curley, Erin, Czerniak, Bogdan, Danilova, Ludmila, Davis, Ian J., Defreitas, Timothy, Demchok, John A., Dhalla, Noreen, Dhir, Rajiv, Doddapaneni, HarshaVardhan, El-Naggar, Adel, Felau, Ina, Ferguson, Martin L., Finocchiaro, Gaetano, Fong, Kwun M., Frazer, Scott, Friedman, William, Fronick, Catrina C., Fulton, Lucinda A., Gabriel, Stacey B., Gao, Jianjiong, Gehlenborg, Nils, Gershenwald, Jeffrey E., Ghossein, Ronald, Giama, Nasra H., Gibbs, Richard A., Gomez, Carmen, Govindan, Ramaswamy, Hayes, D. Neil, Hegde, Apurva M., Heiman, David, I, Heins, Zachary, Hepperla, Austin J., Holbrook, Andrea, Holt, Robert A., Hoyle, Alan P., Hruban, Ralph H., Hu, Jianhong, Huang, Mei, Huntsman, David, Huse, Jason, Donahue, Christine A. Iacobuzio, Ittmann, Michael, Jayaseelan, Joy C., Jefferys, Stuart R., Jones, Corbin D., Jones, Steven J. M., Juhl, Hartmut, Kang, Koo Jeong, Karlan, Beth, Kasaian, Katayoon, Kebebew, Electron, Kim, Hark Kyun, Korchina, Viktoriya, Kundra, Ritika, Lai, Phillip H., Lander, Eric, Le, Xuan, Lee, Darlene, Levine, Douglas A., Lewis, Lora, Ley, Tim, Li, Haiyan Irene, Lin, Pei, Linehan, W. M., Liu, Fei Fei, Lu, Yiling, Lype, Lisa, Ma, Yussanne, Maglinte, Dennis T., Mardis, Elaine R., Marks, Jeffrey, Marra, Marco A., Matthew, Thomas J., Mayo, Michael, McCune, Karen, Meier, Samuel R., Meng, Shaowu, Mieczkowski, Piotr A., Mikkelsen, Tom, Miller, Christopher A., Mills, Gordon B., Moore, Richard A., Morrison, Carl, Mose, Lisle E., Moser, Catherine D., Mungall, Andrew J., Mungall, Karen, Mutch, David, Muzny, Donna M., Myers, Jerome, Newton, Yulia, Noble, Michael S., O'Donnell, Peter, O'Neill, Brian Patrick, Ochoa, Angelica, Park, Joong-Won, Parker, Joel S., Pass, Harvey, Pastore, Alessandro, Pennell, Nathan A., Perou, Charles M., Petrelli, Nicholas, Potapova, Olga, Rader, Janet S., Ramalingam, Suresh, Rathmell, W. Kimryn, Reuter, Victor, Reynolds, Sheila M., Ringel, Matthew, Roach, Jeffrey, Roberts, Lewis R., Robertson, A. Gordon, Sadeghi, Sara, Saller, Charles, Sanchez-Vega, Francisco, Schadendorf, Dirk, Schein, Jacqueline E., Schmidt, Heather K., Schultz, Nikolaus, Seethala, Raja, Senbabaoglu, Yasin, Shelton, Troy, Shi, Yan, Shih, Juliann, Shmulevich, Ilya, Shriver, Craig, Signoretti, Sabina, Simons, Janae, V, Singer, Samuel, Sipahimalani, Payal, Skelly, Tara J., McCune, Karen Smith, Socci, Nicholas D., Soloway, Matthew G., Sood, Anil K., Tam, Angela, Tan, Donghui, Tarnuzzer, Roy, Thiessen, Nina, Thompson, R. Houston, Thorne, Leigh B., Tsao, Ming, Umbricht, Christopher, Van Den Berg, David J., Van Meir, Erwin G., Veluvolu, Umadevi, Voet, Douglas, Wang, Linghua, Weinberger, Paul, Weisenberger, Daniel J., Wigle, Dennis, Wilkerson, Matthew D., Wilson, Richard K., Winterhoff, Boris, Wiznerowicz, Maciej, Wong, Tina, Wong, Winghing, Xi, Liu, Yau, Christina, Zhang, Hailei, Zhang, Hongxin, and Zhang, Jiashan
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).
Published: 2020

12. Resolving medulloblastoma cellular architecture by single-cell genomics

Author: Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Hovestadt, Volker, Smith, Kyle S., Bihannic, Laure, Filbin, Mariella G., Shaw, McKenzie L., Baumgartner, Alicia, DeWitt, John C., Groves, Andrew, Mayr, Lisa, Weisman, Hannah R., Richman, Alyssa R., Shore, Marni E., Goumnerova, Liliana, Rosencrance, Celeste, Carter, Robert A., Phoenix, Timothy N., Hadley, Jennifer L., Tong, Yiai, Houston, Jim, Ashmun, Richard A., DeCuypere, Michael, Sharma, Tanvi, Flasch, Diane, Silkov, Antonina, Ligon, Keith L., Pomeroy, Scott L., Rivera, Miguel N., Rozenblatt-Rosen, Orit, Rusert, Jessica M., Wechsler-Reya, Robert J., Li, Xiao-Nan, Peyrl, Andreas, Gojo, Johannes, Kirchhofer, Dominik, Lötsch, Daniela, Czech, Thomas, Dorfer, Christian, Haberler, Christine, Geyeregger, Rene, Halfmann, Angela, Gawad, Charles, Easton, John, Pfister, Stefan M., Gajjar, Amar, Regev, Aviv, Orr, Brent A., Slavc, Irene, Robinson, Giles W., Bernstein, Bradley E., Suvà, Mario L., Northcott, Paul A., Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Hovestadt, Volker, Smith, Kyle S., Bihannic, Laure, Filbin, Mariella G., Shaw, McKenzie L., Baumgartner, Alicia, DeWitt, John C., Groves, Andrew, Mayr, Lisa, Weisman, Hannah R., Richman, Alyssa R., Shore, Marni E., Goumnerova, Liliana, Rosencrance, Celeste, Carter, Robert A., Phoenix, Timothy N., Hadley, Jennifer L., Tong, Yiai, Houston, Jim, Ashmun, Richard A., DeCuypere, Michael, Sharma, Tanvi, Flasch, Diane, Silkov, Antonina, Ligon, Keith L., Pomeroy, Scott L., Rivera, Miguel N., Rozenblatt-Rosen, Orit, Rusert, Jessica M., Wechsler-Reya, Robert J., Li, Xiao-Nan, Peyrl, Andreas, Gojo, Johannes, Kirchhofer, Dominik, Lötsch, Daniela, Czech, Thomas, Dorfer, Christian, Haberler, Christine, Geyeregger, Rene, Halfmann, Angela, Gawad, Charles, Easton, John, Pfister, Stefan M., Gajjar, Amar, Regev, Aviv, Orr, Brent A., Slavc, Irene, Robinson, Giles W., Bernstein, Bradley E., Suvà, Mario L., and Northcott, Paul A.
Abstract: Medulloblastoma is a malignant childhood cerebellar tumour type that comprises distinct molecular subgroups. Whereas genomic characteristics of these subgroups are well defined, the extent to which cellular diversity underlies their divergent biology and clinical behaviour remains largely unexplored. Here we used single-cell transcriptomics to investigate intra- and intertumoral heterogeneity in 25 medulloblastomas spanning all molecular subgroups. WNT, SHH and Group 3 tumours comprised subgroup-specific undifferentiated and differentiated neuronal-like malignant populations, whereas Group 4 tumours consisted exclusively of differentiated neuronal-like neoplastic cells. SHH tumours closely resembled granule neurons of varying differentiation states that correlated with patient age. Group 3 and Group 4 tumours exhibited a developmental trajectory from primitive progenitor-like to more mature neuronal-like cells, the relative proportions of which distinguished these subgroups. Cross-species transcriptomics defined distinct glutamatergic populations as putative cells-of-origin for SHH and Group 4 subtypes. Collectively, these data provide insights into the cellular and developmental states underlying subtype-specific medulloblastoma biology.
Published: 2020

13. The whole-genome landscape of medulloblastoma subtypes.

Author: Northcott, Paul A, Northcott, Paul A, Buchhalter, Ivo, Morrissy, A Sorana, Hovestadt, Volker, Weischenfeldt, Joachim, Ehrenberger, Tobias, Gröbner, Susanne, Segura-Wang, Maia, Zichner, Thomas, Rudneva, Vasilisa A, Warnatz, Hans-Jörg, Sidiropoulos, Nikos, Phillips, Aaron H, Schumacher, Steven, Kleinheinz, Kortine, Waszak, Sebastian M, Erkek, Serap, Jones, David TW, Worst, Barbara C, Kool, Marcel, Zapatka, Marc, Jäger, Natalie, Chavez, Lukas, Hutter, Barbara, Bieg, Matthias, Paramasivam, Nagarajan, Heinold, Michael, Gu, Zuguang, Ishaque, Naveed, Jäger-Schmidt, Christina, Imbusch, Charles D, Jugold, Alke, Hübschmann, Daniel, Risch, Thomas, Amstislavskiy, Vyacheslav, Gonzalez, Francisco German Rodriguez, Weber, Ursula D, Wolf, Stephan, Robinson, Giles W, Zhou, Xin, Wu, Gang, Finkelstein, David, Liu, Yanling, Cavalli, Florence MG, Luu, Betty, Ramaswamy, Vijay, Wu, Xiaochong, Koster, Jan, Ryzhova, Marina, Cho, Yoon-Jae, Pomeroy, Scott L, Herold-Mende, Christel, Schuhmann, Martin, Ebinger, Martin, Liau, Linda M, Mora, Jaume, McLendon, Roger E, Jabado, Nada, Kumabe, Toshihiro, Chuah, Eric, Ma, Yussanne, Moore, Richard A, Mungall, Andrew J, Mungall, Karen L, Thiessen, Nina, Tse, Kane, Wong, Tina, Jones, Steven JM, Witt, Olaf, Milde, Till, Von Deimling, Andreas, Capper, David, Korshunov, Andrey, Yaspo, Marie-Laure, Kriwacki, Richard, Gajjar, Amar, Zhang, Jinghui, Beroukhim, Rameen, Fraenkel, Ernest, Korbel, Jan O, Brors, Benedikt, Schlesner, Matthias, Eils, Roland, Marra, Marco A, Pfister, Stefan M, Taylor, Michael D, Lichter, Peter, Northcott, Paul A, Northcott, Paul A, Buchhalter, Ivo, Morrissy, A Sorana, Hovestadt, Volker, Weischenfeldt, Joachim, Ehrenberger, Tobias, Gröbner, Susanne, Segura-Wang, Maia, Zichner, Thomas, Rudneva, Vasilisa A, Warnatz, Hans-Jörg, Sidiropoulos, Nikos, Phillips, Aaron H, Schumacher, Steven, Kleinheinz, Kortine, Waszak, Sebastian M, Erkek, Serap, Jones, David TW, Worst, Barbara C, Kool, Marcel, Zapatka, Marc, Jäger, Natalie, Chavez, Lukas, Hutter, Barbara, Bieg, Matthias, Paramasivam, Nagarajan, Heinold, Michael, Gu, Zuguang, Ishaque, Naveed, Jäger-Schmidt, Christina, Imbusch, Charles D, Jugold, Alke, Hübschmann, Daniel, Risch, Thomas, Amstislavskiy, Vyacheslav, Gonzalez, Francisco German Rodriguez, Weber, Ursula D, Wolf, Stephan, Robinson, Giles W, Zhou, Xin, Wu, Gang, Finkelstein, David, Liu, Yanling, Cavalli, Florence MG, Luu, Betty, Ramaswamy, Vijay, Wu, Xiaochong, Koster, Jan, Ryzhova, Marina, Cho, Yoon-Jae, Pomeroy, Scott L, Herold-Mende, Christel, Schuhmann, Martin, Ebinger, Martin, Liau, Linda M, Mora, Jaume, McLendon, Roger E, Jabado, Nada, Kumabe, Toshihiro, Chuah, Eric, Ma, Yussanne, Moore, Richard A, Mungall, Andrew J, Mungall, Karen L, Thiessen, Nina, Tse, Kane, Wong, Tina, Jones, Steven JM, Witt, Olaf, Milde, Till, Von Deimling, Andreas, Capper, David, Korshunov, Andrey, Yaspo, Marie-Laure, Kriwacki, Richard, Gajjar, Amar, Zhang, Jinghui, Beroukhim, Rameen, Fraenkel, Ernest, Korbel, Jan O, Brors, Benedikt, Schlesner, Matthias, Eils, Roland, Marra, Marco A, Pfister, Stefan M, Taylor, Michael D, and Lichter, Peter
Abstract: Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.
Published: 2017

14. The whole-genome landscape of medulloblastoma subtypes.

Author: Northcott, Paul A, Northcott, Paul A, Buchhalter, Ivo, Morrissy, A Sorana, Hovestadt, Volker, Weischenfeldt, Joachim, Ehrenberger, Tobias, Gröbner, Susanne, Segura-Wang, Maia, Zichner, Thomas, Rudneva, Vasilisa A, Warnatz, Hans-Jörg, Sidiropoulos, Nikos, Phillips, Aaron H, Schumacher, Steven, Kleinheinz, Kortine, Waszak, Sebastian M, Erkek, Serap, Jones, David TW, Worst, Barbara C, Kool, Marcel, Zapatka, Marc, Jäger, Natalie, Chavez, Lukas, Hutter, Barbara, Bieg, Matthias, Paramasivam, Nagarajan, Heinold, Michael, Gu, Zuguang, Ishaque, Naveed, Jäger-Schmidt, Christina, Imbusch, Charles D, Jugold, Alke, Hübschmann, Daniel, Risch, Thomas, Amstislavskiy, Vyacheslav, Gonzalez, Francisco German Rodriguez, Weber, Ursula D, Wolf, Stephan, Robinson, Giles W, Zhou, Xin, Wu, Gang, Finkelstein, David, Liu, Yanling, Cavalli, Florence MG, Luu, Betty, Ramaswamy, Vijay, Wu, Xiaochong, Koster, Jan, Ryzhova, Marina, Cho, Yoon-Jae, Pomeroy, Scott L, Herold-Mende, Christel, Schuhmann, Martin, Ebinger, Martin, Liau, Linda M, Mora, Jaume, McLendon, Roger E, Jabado, Nada, Kumabe, Toshihiro, Chuah, Eric, Ma, Yussanne, Moore, Richard A, Mungall, Andrew J, Mungall, Karen L, Thiessen, Nina, Tse, Kane, Wong, Tina, Jones, Steven JM, Witt, Olaf, Milde, Till, Von Deimling, Andreas, Capper, David, Korshunov, Andrey, Yaspo, Marie-Laure, Kriwacki, Richard, Gajjar, Amar, Zhang, Jinghui, Beroukhim, Rameen, Fraenkel, Ernest, Korbel, Jan O, Brors, Benedikt, Schlesner, Matthias, Eils, Roland, Marra, Marco A, Pfister, Stefan M, Taylor, Michael D, Lichter, Peter, Northcott, Paul A, Northcott, Paul A, Buchhalter, Ivo, Morrissy, A Sorana, Hovestadt, Volker, Weischenfeldt, Joachim, Ehrenberger, Tobias, Gröbner, Susanne, Segura-Wang, Maia, Zichner, Thomas, Rudneva, Vasilisa A, Warnatz, Hans-Jörg, Sidiropoulos, Nikos, Phillips, Aaron H, Schumacher, Steven, Kleinheinz, Kortine, Waszak, Sebastian M, Erkek, Serap, Jones, David TW, Worst, Barbara C, Kool, Marcel, Zapatka, Marc, Jäger, Natalie, Chavez, Lukas, Hutter, Barbara, Bieg, Matthias, Paramasivam, Nagarajan, Heinold, Michael, Gu, Zuguang, Ishaque, Naveed, Jäger-Schmidt, Christina, Imbusch, Charles D, Jugold, Alke, Hübschmann, Daniel, Risch, Thomas, Amstislavskiy, Vyacheslav, Gonzalez, Francisco German Rodriguez, Weber, Ursula D, Wolf, Stephan, Robinson, Giles W, Zhou, Xin, Wu, Gang, Finkelstein, David, Liu, Yanling, Cavalli, Florence MG, Luu, Betty, Ramaswamy, Vijay, Wu, Xiaochong, Koster, Jan, Ryzhova, Marina, Cho, Yoon-Jae, Pomeroy, Scott L, Herold-Mende, Christel, Schuhmann, Martin, Ebinger, Martin, Liau, Linda M, Mora, Jaume, McLendon, Roger E, Jabado, Nada, Kumabe, Toshihiro, Chuah, Eric, Ma, Yussanne, Moore, Richard A, Mungall, Andrew J, Mungall, Karen L, Thiessen, Nina, Tse, Kane, Wong, Tina, Jones, Steven JM, Witt, Olaf, Milde, Till, Von Deimling, Andreas, Capper, David, Korshunov, Andrey, Yaspo, Marie-Laure, Kriwacki, Richard, Gajjar, Amar, Zhang, Jinghui, Beroukhim, Rameen, Fraenkel, Ernest, Korbel, Jan O, Brors, Benedikt, Schlesner, Matthias, Eils, Roland, Marra, Marco A, Pfister, Stefan M, Taylor, Michael D, and Lichter, Peter
Abstract: Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.
Published: 2017

15. Lsd1 as a therapeutic target in Gfi1-activated medulloblastoma.

Author: Lee, Catherine, Lee, Catherine, Rudneva, Vasilisa A, Erkek, Serap, Zapatka, Marc, Chau, Lianne Q, Tacheva-Grigorova, Silvia K, Garancher, Alexandra, Rusert, Jessica M, Aksoy, Ozlem, Lea, Robin, Mohammad, Helai P, Wang, Jianxun, Weiss, William A, Grimes, H Leighton, Pfister, Stefan M, Northcott, Paul A, Wechsler-Reya, Robert J, Lee, Catherine, Lee, Catherine, Rudneva, Vasilisa A, Erkek, Serap, Zapatka, Marc, Chau, Lianne Q, Tacheva-Grigorova, Silvia K, Garancher, Alexandra, Rusert, Jessica M, Aksoy, Ozlem, Lea, Robin, Mohammad, Helai P, Wang, Jianxun, Weiss, William A, Grimes, H Leighton, Pfister, Stefan M, Northcott, Paul A, and Wechsler-Reya, Robert J
Abstract: Drugs that modify the epigenome are powerful tools for treating cancer, but these drugs often have pleiotropic effects, and identifying patients who will benefit from them remains a major clinical challenge. Here we show that medulloblastomas driven by the transcription factor Gfi1 are exquisitely dependent on the enzyme lysine demethylase 1 (Kdm1a/Lsd1). We demonstrate that Lsd1 physically associates with Gfi1, and that these proteins cooperate to inhibit genes involved in neuronal commitment and differentiation. We also show that Lsd1 is essential for Gfi1-mediated transformation: Gfi1 proteins that cannot recruit Lsd1 are unable to drive tumorigenesis, and genetic ablation of Lsd1 markedly impairs tumor growth in vivo. Finally, pharmacological inhibitors of Lsd1 potently inhibit growth of Gfi1-driven tumors. These studies provide important insight into the mechanisms by which Gfi1 contributes to tumorigenesis, and identify Lsd1 inhibitors as promising therapeutic agents for Gfi1-driven medulloblastoma.
Published: 2019

16. Lsd1 as a therapeutic target in Gfi1-activated medulloblastoma.

Author: Lee, Catherine, Lee, Catherine, Rudneva, Vasilisa A, Erkek, Serap, Zapatka, Marc, Chau, Lianne Q, Tacheva-Grigorova, Silvia K, Garancher, Alexandra, Rusert, Jessica M, Aksoy, Ozlem, Lea, Robin, Mohammad, Helai P, Wang, Jianxun, Weiss, William A, Grimes, H Leighton, Pfister, Stefan M, Northcott, Paul A, Wechsler-Reya, Robert J, Lee, Catherine, Lee, Catherine, Rudneva, Vasilisa A, Erkek, Serap, Zapatka, Marc, Chau, Lianne Q, Tacheva-Grigorova, Silvia K, Garancher, Alexandra, Rusert, Jessica M, Aksoy, Ozlem, Lea, Robin, Mohammad, Helai P, Wang, Jianxun, Weiss, William A, Grimes, H Leighton, Pfister, Stefan M, Northcott, Paul A, and Wechsler-Reya, Robert J
Abstract: Drugs that modify the epigenome are powerful tools for treating cancer, but these drugs often have pleiotropic effects, and identifying patients who will benefit from them remains a major clinical challenge. Here we show that medulloblastomas driven by the transcription factor Gfi1 are exquisitely dependent on the enzyme lysine demethylase 1 (Kdm1a/Lsd1). We demonstrate that Lsd1 physically associates with Gfi1, and that these proteins cooperate to inhibit genes involved in neuronal commitment and differentiation. We also show that Lsd1 is essential for Gfi1-mediated transformation: Gfi1 proteins that cannot recruit Lsd1 are unable to drive tumorigenesis, and genetic ablation of Lsd1 markedly impairs tumor growth in vivo. Finally, pharmacological inhibitors of Lsd1 potently inhibit growth of Gfi1-driven tumors. These studies provide important insight into the mechanisms by which Gfi1 contributes to tumorigenesis, and identify Lsd1 inhibitors as promising therapeutic agents for Gfi1-driven medulloblastoma.
Published: 2019

17. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.

Author: Waszak, Sebastian M, Waszak, Sebastian M, Northcott, Paul A, Buchhalter, Ivo, Robinson, Giles W, Sutter, Christian, Groebner, Susanne, Grund, Kerstin B, Brugières, Laurence, Jones, David TW, Pajtler, Kristian W, Morrissy, A Sorana, Kool, Marcel, Sturm, Dominik, Chavez, Lukas, Ernst, Aurelie, Brabetz, Sebastian, Hain, Michael, Zichner, Thomas, Segura-Wang, Maia, Weischenfeldt, Joachim, Rausch, Tobias, Mardin, Balca R, Zhou, Xin, Baciu, Cristina, Lawerenz, Christian, Chan, Jennifer A, Varlet, Pascale, Guerrini-Rousseau, Lea, Fults, Daniel W, Grajkowska, Wiesława, Hauser, Peter, Jabado, Nada, Ra, Young-Shin, Zitterbart, Karel, Shringarpure, Suyash S, De La Vega, Francisco M, Bustamante, Carlos D, Ng, Ho-Keung, Perry, Arie, MacDonald, Tobey J, Hernáiz Driever, Pablo, Bendel, Anne E, Bowers, Daniel C, McCowage, Geoffrey, Chintagumpala, Murali M, Cohn, Richard, Hassall, Timothy, Fleischhack, Gudrun, Eggen, Tone, Wesenberg, Finn, Feychting, Maria, Lannering, Birgitta, Schüz, Joachim, Johansen, Christoffer, Andersen, Tina V, Röösli, Martin, Kuehni, Claudia E, Grotzer, Michael, Kjaerheim, Kristina, Monoranu, Camelia M, Archer, Tenley C, Duke, Elizabeth, Pomeroy, Scott L, Shelagh, Redmond, Frank, Stephan, Sumerauer, David, Scheurlen, Wolfram, Ryzhova, Marina V, Milde, Till, Kratz, Christian P, Samuel, David, Zhang, Jinghui, Solomon, David A, Marra, Marco, Eils, Roland, Bartram, Claus R, von Hoff, Katja, Rutkowski, Stefan, Ramaswamy, Vijay, Gilbertson, Richard J, Korshunov, Andrey, Taylor, Michael D, Lichter, Peter, Malkin, David, Gajjar, Amar, Korbel, Jan O, Pfister, Stefan M, Waszak, Sebastian M, Waszak, Sebastian M, Northcott, Paul A, Buchhalter, Ivo, Robinson, Giles W, Sutter, Christian, Groebner, Susanne, Grund, Kerstin B, Brugières, Laurence, Jones, David TW, Pajtler, Kristian W, Morrissy, A Sorana, Kool, Marcel, Sturm, Dominik, Chavez, Lukas, Ernst, Aurelie, Brabetz, Sebastian, Hain, Michael, Zichner, Thomas, Segura-Wang, Maia, Weischenfeldt, Joachim, Rausch, Tobias, Mardin, Balca R, Zhou, Xin, Baciu, Cristina, Lawerenz, Christian, Chan, Jennifer A, Varlet, Pascale, Guerrini-Rousseau, Lea, Fults, Daniel W, Grajkowska, Wiesława, Hauser, Peter, Jabado, Nada, Ra, Young-Shin, Zitterbart, Karel, Shringarpure, Suyash S, De La Vega, Francisco M, Bustamante, Carlos D, Ng, Ho-Keung, Perry, Arie, MacDonald, Tobey J, Hernáiz Driever, Pablo, Bendel, Anne E, Bowers, Daniel C, McCowage, Geoffrey, Chintagumpala, Murali M, Cohn, Richard, Hassall, Timothy, Fleischhack, Gudrun, Eggen, Tone, Wesenberg, Finn, Feychting, Maria, Lannering, Birgitta, Schüz, Joachim, Johansen, Christoffer, Andersen, Tina V, Röösli, Martin, Kuehni, Claudia E, Grotzer, Michael, Kjaerheim, Kristina, Monoranu, Camelia M, Archer, Tenley C, Duke, Elizabeth, Pomeroy, Scott L, Shelagh, Redmond, Frank, Stephan, Sumerauer, David, Scheurlen, Wolfram, Ryzhova, Marina V, Milde, Till, Kratz, Christian P, Samuel, David, Zhang, Jinghui, Solomon, David A, Marra, Marco, Eils, Roland, Bartram, Claus R, von Hoff, Katja, Rutkowski, Stefan, Ramaswamy, Vijay, Gilbertson, Richard J, Korshunov, Andrey, Taylor, Michael D, Lichter, Peter, Malkin, David, Gajjar, Amar, Korbel, Jan O, and Pfister, Stefan M
Abstract: BackgroundMedulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines.MethodsIn this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma.FindingsWe included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these aga
Published: 2018

18. Deep sequencing of WNT-activated medulloblastomas reveals secondary SHH pathway activation.

Author: Iorgulescu, J Bryan, Iorgulescu, J Bryan, Van Ziffle, Jessica, Stevers, Meredith, Grenert, James P, Bastian, Boris C, Chavez, Lukas, Stichel, Damian, Buchhalter, Ivo, Samuel, David, Nicolaides, Theodore, Banerjee, Anuradha, Mueller, Sabine, Gupta, Nalin, Tihan, Tarik, Bollen, Andrew W, Northcott, Paul A, Kool, Marcel, Pfister, Stefan, Korshunov, Andrey, Perry, Arie, Solomon, David A, Iorgulescu, J Bryan, Iorgulescu, J Bryan, Van Ziffle, Jessica, Stevers, Meredith, Grenert, James P, Bastian, Boris C, Chavez, Lukas, Stichel, Damian, Buchhalter, Ivo, Samuel, David, Nicolaides, Theodore, Banerjee, Anuradha, Mueller, Sabine, Gupta, Nalin, Tihan, Tarik, Bollen, Andrew W, Northcott, Paul A, Kool, Marcel, Pfister, Stefan, Korshunov, Andrey, Perry, Arie, and Solomon, David A
Published: 2018

19. DNA methylation-based classification of central nervous system tumours

Author: Capper, David, Jones, David T.W., Sill, Martin, Hovestadt, Volker, Schrimpf, Daniel, Sturm, Dominik, Koelsche, Christian, Sahm, Felix, Chavez, Lukas, Reuss, David E., Kratz, Annekathrin, Wefers, Annika K., Huang, Kristin, Pajtler, Kristian W., Schweizer, Leonille, Stichel, Damian, Olar, Adriana, Engel, Nils W., Lindenberg, Kerstin, Harter, Patrick N., Braczynski, Anne K., Plate, Karl H., Dohmen, Hildegard, Garvalov, Boyan K., Coras, Roland, Hölsken, Annett, Hewer, Ekkehard, Bewerunge-Hudler, Melanie, Schick, Matthias, Fischer, Roger, Beschorner, Rudi, Schittenhelm, Jens, Staszewski, Ori, Wani, Khalida, Varlet, Pascale, Pages, Melanie, Temming, Petra, Lohmann, Dietmar, Selt, Florian, Witt, Hendrik, Milde, Till, Witt, Olaf, Aronica, Eleonora, Giangaspero, Felice, Rushing, Elisabeth, Scheurlen, Wolfram, Geisenberger, Christoph, Rodriguez, Fausto J., Becker, Albert, Preusser, Matthias, Haberler, Christine, Bjerkvig, Rolf, Cryan, Jane, Farrell, Michael, Deckert, Martina, Hench, Jürgen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brück, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Hänggi, Daniel, Hans, Volkmar, Rozsnoki, Stephanie, Hansford, Jordan R., Kohlhof, Patricia, Kristensen, Bjarne W., Lechner, Matt, Lopes, Beatriz, Mawrin, Christian, Ketter, Ralf, Kulozik, Andreas, Khatib, Ziad, Heppner, Frank, Koch, Arend, Jouvet, Anne, Keohane, Catherine, Mühleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G., Driever, Pablo Hernáiz, Kramm, Christof M., Müller, Hermann L., Rutkowski, Stefan, Von Hoff, Katja, Frühwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia Maria, Perry, Arie, Jones, Chris, Jacques, Thomas S., Radlwimmer, Bernhard, Gessi, Marco, Pietsch, Torsten, Schramm, Johannes, Schackert, Gabriele, Westphal, Manfred, Reifenberger, Guido, Wesseling, Pieter, Weller, Michael, Collins, Vincent Peter, Blümcke, Ingmar, Bendszus, Martin, Debus, Jürgen, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Robinson, Giles W., Taylor, Michael D., Jaunmuktane, Zane, Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Karajannis, Matthias A., Mittelbronn, Michel, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Schüller, Ulrich, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Brandner, Sebastian, Korshunov, Andrey, Von Deimling, Andreas, Pfister, Stefan M., Capper, David, Jones, David T.W., Sill, Martin, Hovestadt, Volker, Schrimpf, Daniel, Sturm, Dominik, Koelsche, Christian, Sahm, Felix, Chavez, Lukas, Reuss, David E., Kratz, Annekathrin, Wefers, Annika K., Huang, Kristin, Pajtler, Kristian W., Schweizer, Leonille, Stichel, Damian, Olar, Adriana, Engel, Nils W., Lindenberg, Kerstin, Harter, Patrick N., Braczynski, Anne K., Plate, Karl H., Dohmen, Hildegard, Garvalov, Boyan K., Coras, Roland, Hölsken, Annett, Hewer, Ekkehard, Bewerunge-Hudler, Melanie, Schick, Matthias, Fischer, Roger, Beschorner, Rudi, Schittenhelm, Jens, Staszewski, Ori, Wani, Khalida, Varlet, Pascale, Pages, Melanie, Temming, Petra, Lohmann, Dietmar, Selt, Florian, Witt, Hendrik, Milde, Till, Witt, Olaf, Aronica, Eleonora, Giangaspero, Felice, Rushing, Elisabeth, Scheurlen, Wolfram, Geisenberger, Christoph, Rodriguez, Fausto J., Becker, Albert, Preusser, Matthias, Haberler, Christine, Bjerkvig, Rolf, Cryan, Jane, Farrell, Michael, Deckert, Martina, Hench, Jürgen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brück, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Hänggi, Daniel, Hans, Volkmar, Rozsnoki, Stephanie, Hansford, Jordan R., Kohlhof, Patricia, Kristensen, Bjarne W., Lechner, Matt, Lopes, Beatriz, Mawrin, Christian, Ketter, Ralf, Kulozik, Andreas, Khatib, Ziad, Heppner, Frank, Koch, Arend, Jouvet, Anne, Keohane, Catherine, Mühleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G., Driever, Pablo Hernáiz, Kramm, Christof M., Müller, Hermann L., Rutkowski, Stefan, Von Hoff, Katja, Frühwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia Maria, Perry, Arie, Jones, Chris, Jacques, Thomas S., Radlwimmer, Bernhard, Gessi, Marco, Pietsch, Torsten, Schramm, Johannes, Schackert, Gabriele, Westphal, Manfred, Reifenberger, Guido, Wesseling, Pieter, Weller, Michael, Collins, Vincent Peter, Blümcke, Ingmar, Bendszus, Martin, Debus, Jürgen, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Robinson, Giles W., Taylor, Michael D., Jaunmuktane, Zane, Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Karajannis, Matthias A., Mittelbronn, Michel, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Schüller, Ulrich, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Brandner, Sebastian, Korshunov, Andrey, Von Deimling, Andreas, and Pfister, Stefan M.
Published: 2018

20. DNA methylation-based classification of central nervous system tumours

Author: Capper, David, Jones, David T.W., Sill, Martin, Hovestadt, Volker, Schrimpf, Daniel, Sturm, Dominik, Koelsche, Christian, Sahm, Felix, Chavez, Lukas, Reuss, David E., Kratz, Annekathrin, Wefers, Annika K., Huang, Kristin, Pajtler, Kristian W., Schweizer, Leonille, Stichel, Damian, Olar, Adriana, Engel, Nils W., Lindenberg, Kerstin, Harter, Patrick N., Braczynski, Anne K., Plate, Karl H., Dohmen, Hildegard, Garvalov, Boyan K., Coras, Roland, Hölsken, Annett, Hewer, Ekkehard, Bewerunge-Hudler, Melanie, Schick, Matthias, Fischer, Roger, Beschorner, Rudi, Schittenhelm, Jens, Staszewski, Ori, Wani, Khalida, Varlet, Pascale, Pages, Melanie, Temming, Petra, Lohmann, Dietmar, Selt, Florian, Witt, Hendrik, Milde, Till, Witt, Olaf, Aronica, Eleonora, Giangaspero, Felice, Rushing, Elisabeth, Scheurlen, Wolfram, Geisenberger, Christoph, Rodriguez, Fausto J., Becker, Albert, Preusser, Matthias, Haberler, Christine, Bjerkvig, Rolf, Cryan, Jane, Farrell, Michael, Deckert, Martina, Hench, Jürgen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brück, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Hänggi, Daniel, Hans, Volkmar, Rozsnoki, Stephanie, Hansford, Jordan R., Kohlhof, Patricia, Kristensen, Bjarne W., Lechner, Matt, Lopes, Beatriz, Mawrin, Christian, Ketter, Ralf, Kulozik, Andreas, Khatib, Ziad, Heppner, Frank, Koch, Arend, Jouvet, Anne, Keohane, Catherine, Mühleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G., Driever, Pablo Hernáiz, Kramm, Christof M., Müller, Hermann L., Rutkowski, Stefan, Von Hoff, Katja, Frühwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia Maria, Perry, Arie, Jones, Chris, Jacques, Thomas S., Radlwimmer, Bernhard, Gessi, Marco, Pietsch, Torsten, Schramm, Johannes, Schackert, Gabriele, Westphal, Manfred, Reifenberger, Guido, Wesseling, Pieter, Weller, Michael, Collins, Vincent Peter, Blümcke, Ingmar, Bendszus, Martin, Debus, Jürgen, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Robinson, Giles W., Taylor, Michael D., Jaunmuktane, Zane, Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Karajannis, Matthias A., Mittelbronn, Michel, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Schüller, Ulrich, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Brandner, Sebastian, Korshunov, Andrey, Von Deimling, Andreas, Pfister, Stefan M., Capper, David, Jones, David T.W., Sill, Martin, Hovestadt, Volker, Schrimpf, Daniel, Sturm, Dominik, Koelsche, Christian, Sahm, Felix, Chavez, Lukas, Reuss, David E., Kratz, Annekathrin, Wefers, Annika K., Huang, Kristin, Pajtler, Kristian W., Schweizer, Leonille, Stichel, Damian, Olar, Adriana, Engel, Nils W., Lindenberg, Kerstin, Harter, Patrick N., Braczynski, Anne K., Plate, Karl H., Dohmen, Hildegard, Garvalov, Boyan K., Coras, Roland, Hölsken, Annett, Hewer, Ekkehard, Bewerunge-Hudler, Melanie, Schick, Matthias, Fischer, Roger, Beschorner, Rudi, Schittenhelm, Jens, Staszewski, Ori, Wani, Khalida, Varlet, Pascale, Pages, Melanie, Temming, Petra, Lohmann, Dietmar, Selt, Florian, Witt, Hendrik, Milde, Till, Witt, Olaf, Aronica, Eleonora, Giangaspero, Felice, Rushing, Elisabeth, Scheurlen, Wolfram, Geisenberger, Christoph, Rodriguez, Fausto J., Becker, Albert, Preusser, Matthias, Haberler, Christine, Bjerkvig, Rolf, Cryan, Jane, Farrell, Michael, Deckert, Martina, Hench, Jürgen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brück, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Hänggi, Daniel, Hans, Volkmar, Rozsnoki, Stephanie, Hansford, Jordan R., Kohlhof, Patricia, Kristensen, Bjarne W., Lechner, Matt, Lopes, Beatriz, Mawrin, Christian, Ketter, Ralf, Kulozik, Andreas, Khatib, Ziad, Heppner, Frank, Koch, Arend, Jouvet, Anne, Keohane, Catherine, Mühleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G., Driever, Pablo Hernáiz, Kramm, Christof M., Müller, Hermann L., Rutkowski, Stefan, Von Hoff, Katja, Frühwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia Maria, Perry, Arie, Jones, Chris, Jacques, Thomas S., Radlwimmer, Bernhard, Gessi, Marco, Pietsch, Torsten, Schramm, Johannes, Schackert, Gabriele, Westphal, Manfred, Reifenberger, Guido, Wesseling, Pieter, Weller, Michael, Collins, Vincent Peter, Blümcke, Ingmar, Bendszus, Martin, Debus, Jürgen, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Robinson, Giles W., Taylor, Michael D., Jaunmuktane, Zane, Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Karajannis, Matthias A., Mittelbronn, Michel, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Schüller, Ulrich, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Brandner, Sebastian, Korshunov, Andrey, Von Deimling, Andreas, and Pfister, Stefan M.
Published: 2018

21. DNA methylation-based classification of central nervous system tumours

Author: Capper, David, Jones, David T. W., Sill, Martin, Hovestadt, Volker, Schrimpf, Daniel, Sturm, Dominik, Koelsche, Christian, Sahm, Felix, Chavez, Lukas, Reuss, David E., Kratz, Annekathrin, Wefers, Annika K., Huang, Kristin, Pajtler, Kristian W., Schweizer, Leonille, Stichel, Damian, Olar, Adriana, Engel, Nils W., Lindenberg, Kerstin, Harter, Patrick N., Braczynski, Anne K., Plate, Karl H., Dohmen, Hildegard, Garvalov, Boyan K., Coras, Roland, Hoelsken, Annett, Hewer, Ekkehard, Bewerunge-Hudler, Melanie, Schick, Matthias, Fischer, Roger, Beschorner, Rudi, Schittenhelm, Jens, Staszewski, Ori, Wani, Khalida, Varlet, Pascale, Pages, Melanie, Temming, Petra, Lohmann, Dietmar, Selt, Florian, Witt, Hendrik, Milde, Till, Witt, Olaf, Aronica, Eleonora, Giangaspero, Felice, Rushing, Elisabeth, Scheurlen, Wolfram, Geisenberger, Christoph, Rodriguez, Fausto J., Becker, Albert, Preusser, Matthias, Haberler, Christine, Bjerkvig, Rolf, Cryan, Jane, Farrell, Michael, Deckert, Martina, Hench, Juergen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brueck, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Haenggi, Daniel, Hans, Volkmar, Rozsnoki, Stephanie, Hansford, Jordan R., Kohlhof, Patricia, Kristensen, Bjarne W., Lechner, Matt, Lopes, Beatriz, Mawrin, Christian, Ketter, Ralf, Kulozik, Andreas, Khatib, Ziad, Heppner, Frank, Koch, Arend, Jouvet, Anne, Keohane, Catherine, Muehleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G., Driever, Pablo Hernaiz, Kramm, Christof M., Mueller, Hermann L., Rutkowski, Stefan, von Hoff, Katja, Fruehwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia-Maria, Perry, Arie, Jones, Chris, Jacques, Thomas S., Radlwimmer, Bernhard, Gessi, Marco, Pietsch, Torsten, Schramm, Johannes, Schackert, Gabriele, Westphal, Manfred, Reifenberger, Guido, Wesseling, Pieter, Weller, Michael, Collins, Vincent Peter, Bluemcke, Ingmar, Bendszus, Martin, Debus, Juergen, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Robinson, Giles W., Taylor, Michael D., Jaunmuktane, Zane, Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Karajannis, Matthias A., Mittelbronn, Michel, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Schueller, Ulrich, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Brandner, Sebastian, Korshunov, Andrey, von Deimling, Andreas, Pfister, Stefan M., Capper, David, Jones, David T. W., Sill, Martin, Hovestadt, Volker, Schrimpf, Daniel, Sturm, Dominik, Koelsche, Christian, Sahm, Felix, Chavez, Lukas, Reuss, David E., Kratz, Annekathrin, Wefers, Annika K., Huang, Kristin, Pajtler, Kristian W., Schweizer, Leonille, Stichel, Damian, Olar, Adriana, Engel, Nils W., Lindenberg, Kerstin, Harter, Patrick N., Braczynski, Anne K., Plate, Karl H., Dohmen, Hildegard, Garvalov, Boyan K., Coras, Roland, Hoelsken, Annett, Hewer, Ekkehard, Bewerunge-Hudler, Melanie, Schick, Matthias, Fischer, Roger, Beschorner, Rudi, Schittenhelm, Jens, Staszewski, Ori, Wani, Khalida, Varlet, Pascale, Pages, Melanie, Temming, Petra, Lohmann, Dietmar, Selt, Florian, Witt, Hendrik, Milde, Till, Witt, Olaf, Aronica, Eleonora, Giangaspero, Felice, Rushing, Elisabeth, Scheurlen, Wolfram, Geisenberger, Christoph, Rodriguez, Fausto J., Becker, Albert, Preusser, Matthias, Haberler, Christine, Bjerkvig, Rolf, Cryan, Jane, Farrell, Michael, Deckert, Martina, Hench, Juergen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brueck, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Haenggi, Daniel, Hans, Volkmar, Rozsnoki, Stephanie, Hansford, Jordan R., Kohlhof, Patricia, Kristensen, Bjarne W., Lechner, Matt, Lopes, Beatriz, Mawrin, Christian, Ketter, Ralf, Kulozik, Andreas, Khatib, Ziad, Heppner, Frank, Koch, Arend, Jouvet, Anne, Keohane, Catherine, Muehleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G., Driever, Pablo Hernaiz, Kramm, Christof M., Mueller, Hermann L., Rutkowski, Stefan, von Hoff, Katja, Fruehwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia-Maria, Perry, Arie, Jones, Chris, Jacques, Thomas S., Radlwimmer, Bernhard, Gessi, Marco, Pietsch, Torsten, Schramm, Johannes, Schackert, Gabriele, Westphal, Manfred, Reifenberger, Guido, Wesseling, Pieter, Weller, Michael, Collins, Vincent Peter, Bluemcke, Ingmar, Bendszus, Martin, Debus, Juergen, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Robinson, Giles W., Taylor, Michael D., Jaunmuktane, Zane, Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Karajannis, Matthias A., Mittelbronn, Michel, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Schueller, Ulrich, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Brandner, Sebastian, Korshunov, Andrey, von Deimling, Andreas, and Pfister, Stefan M.
Abstract: Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challengingwith substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.
Published: 2018

22. The landscape of genomic alterations across childhood cancers

Author: Groebner, Susanne N., Worst, Barbara C., Weischenfeldt, Joachim, Buchhalter, Ivo, Kleinheinz, Kortine, Rudneva, Vasilisa A., Johann, Pascal D., Balasubramanian, Gnana Prakash, Segura-Wang, Maia, Brabetz, Sebastian, Bender, Sebastian, Hutter, Barbara, Sturm, Dominik, Pfaff, Elke, Huebschmann, Daniel, Zipprich, Gideon, Heinold, Michael, Eils, Jurgen, Lawerenz, Christian, Erkek, Serap, Lambo, Sander, Waszak, Sebastian, Blattmann, Claudia, Borkhardt, Arndt, Kuhlen, Michaela, Eggert, Angelika, Fulda, Simone, Gessler, Manfred, Wegert, Jenny, Kappler, Roland, Baumhoer, Daniel, Burdach, Stefan, Kirschner-Schwabe, Renate, Kontny, Udo, Kulozik, Andreas E., Lohmann, Dietmar, Hettmer, Simone, Eckert, Cornelia, Bielack, Stefan, Nathrath, Michaela, Niemeyer, Charlotte, Richter, Gunther H., Schulte, Johannes, Siebert, Reiner, Westermann, Frank, Molenaar, Jan J., Vassal, Gilles, Witt, Hendrik, Burkhardt, Birgit, Kratz, Christian P., Witt, Olaf, van Tilburg, Cornelis M., Kramm, Christof M., Fleischhack, Gudrun, Dirksen, Uta, Rutkowski, Stefan, Fruhwald, Michael, von Hoff, Katja, Wolf, Stephan, Klingebiel, Thomas, Koscielniak, Ewa, Landgraf, Pablo, Koster, Jan, Resnick, Adam C., Zhang, Jinghui, Liu, Yanling, Zhou, Xin, Waanders, Angela J., Zwijnenburg, Danny A., Raman, Pichai, Brors, Benedikt, Weber, Ursula D., Northcott, Paul A., Pajtler, Kristian W., Kool, Marcel, Piro, Rosario M., Korbel, Jan O., Schlesner, Matthias, Eils, Roland, Jones, David T. W., Lichter, Peter, Chavez, Lukas, Zapatka, Marc, Pfister, Stefan M., Groebner, Susanne N., Worst, Barbara C., Weischenfeldt, Joachim, Buchhalter, Ivo, Kleinheinz, Kortine, Rudneva, Vasilisa A., Johann, Pascal D., Balasubramanian, Gnana Prakash, Segura-Wang, Maia, Brabetz, Sebastian, Bender, Sebastian, Hutter, Barbara, Sturm, Dominik, Pfaff, Elke, Huebschmann, Daniel, Zipprich, Gideon, Heinold, Michael, Eils, Jurgen, Lawerenz, Christian, Erkek, Serap, Lambo, Sander, Waszak, Sebastian, Blattmann, Claudia, Borkhardt, Arndt, Kuhlen, Michaela, Eggert, Angelika, Fulda, Simone, Gessler, Manfred, Wegert, Jenny, Kappler, Roland, Baumhoer, Daniel, Burdach, Stefan, Kirschner-Schwabe, Renate, Kontny, Udo, Kulozik, Andreas E., Lohmann, Dietmar, Hettmer, Simone, Eckert, Cornelia, Bielack, Stefan, Nathrath, Michaela, Niemeyer, Charlotte, Richter, Gunther H., Schulte, Johannes, Siebert, Reiner, Westermann, Frank, Molenaar, Jan J., Vassal, Gilles, Witt, Hendrik, Burkhardt, Birgit, Kratz, Christian P., Witt, Olaf, van Tilburg, Cornelis M., Kramm, Christof M., Fleischhack, Gudrun, Dirksen, Uta, Rutkowski, Stefan, Fruhwald, Michael, von Hoff, Katja, Wolf, Stephan, Klingebiel, Thomas, Koscielniak, Ewa, Landgraf, Pablo, Koster, Jan, Resnick, Adam C., Zhang, Jinghui, Liu, Yanling, Zhou, Xin, Waanders, Angela J., Zwijnenburg, Danny A., Raman, Pichai, Brors, Benedikt, Weber, Ursula D., Northcott, Paul A., Pajtler, Kristian W., Kool, Marcel, Piro, Rosario M., Korbel, Jan O., Schlesner, Matthias, Eils, Roland, Jones, David T. W., Lichter, Peter, Chavez, Lukas, Zapatka, Marc, and Pfister, Stefan M.
Abstract: Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7-8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.
Published: 2018

23. Deep sequencing of WNT-activated medulloblastomas reveals secondary SHH pathway activation.

Author: Iorgulescu, J Bryan, Iorgulescu, J Bryan, Van Ziffle, Jessica, Stevers, Meredith, Grenert, James P, Bastian, Boris C, Chavez, Lukas, Stichel, Damian, Buchhalter, Ivo, Samuel, David, Nicolaides, Theodore, Banerjee, Anuradha, Mueller, Sabine, Gupta, Nalin, Tihan, Tarik, Bollen, Andrew W, Northcott, Paul A, Kool, Marcel, Pfister, Stefan, Korshunov, Andrey, Perry, Arie, Solomon, David A, Iorgulescu, J Bryan, Iorgulescu, J Bryan, Van Ziffle, Jessica, Stevers, Meredith, Grenert, James P, Bastian, Boris C, Chavez, Lukas, Stichel, Damian, Buchhalter, Ivo, Samuel, David, Nicolaides, Theodore, Banerjee, Anuradha, Mueller, Sabine, Gupta, Nalin, Tihan, Tarik, Bollen, Andrew W, Northcott, Paul A, Kool, Marcel, Pfister, Stefan, Korshunov, Andrey, Perry, Arie, and Solomon, David A
Published: 2018

24. DNA methylation-based classification of central nervous system tumours

Author: Capper, David, Jones, David T.W., Sill, Martin, Hovestadt, Volker, Schrimpf, Daniel, Sturm, Dominik, Koelsche, Christian, Sahm, Felix, Chavez, Lukas, Reuss, David E., Kratz, Annekathrin, Wefers, Annika K., Huang, Kristin, Pajtler, Kristian W., Schweizer, Leonille, Stichel, Damian, Olar, Adriana, Engel, Nils W., Lindenberg, Kerstin, Harter, Patrick N., Braczynski, Anne K., Plate, Karl H., Dohmen, Hildegard, Garvalov, Boyan K., Coras, Roland, Hölsken, Annett, Hewer, Ekkehard, Bewerunge-Hudler, Melanie, Schick, Matthias, Fischer, Roger, Beschorner, Rudi, Schittenhelm, Jens, Staszewski, Ori, Wani, Khalida, Varlet, Pascale, Pages, Melanie, Temming, Petra, Lohmann, Dietmar, Selt, Florian, Witt, Hendrik, Milde, Till, Witt, Olaf, Aronica, Eleonora, Giangaspero, Felice, Rushing, Elisabeth, Scheurlen, Wolfram, Geisenberger, Christoph, Rodriguez, Fausto J., Becker, Albert, Preusser, Matthias, Haberler, Christine, Bjerkvig, Rolf, Cryan, Jane, Farrell, Michael, Deckert, Martina, Hench, Jürgen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brück, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Hänggi, Daniel, Hans, Volkmar, Rozsnoki, Stephanie, Hansford, Jordan R., Kohlhof, Patricia, Kristensen, Bjarne W., Lechner, Matt, Lopes, Beatriz, Mawrin, Christian, Ketter, Ralf, Kulozik, Andreas, Khatib, Ziad, Heppner, Frank, Koch, Arend, Jouvet, Anne, Keohane, Catherine, Mühleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G., Driever, Pablo Hernáiz, Kramm, Christof M., Müller, Hermann L., Rutkowski, Stefan, Von Hoff, Katja, Frühwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia Maria, Perry, Arie, Jones, Chris, Jacques, Thomas S., Radlwimmer, Bernhard, Gessi, Marco, Pietsch, Torsten, Schramm, Johannes, Schackert, Gabriele, Westphal, Manfred, Reifenberger, Guido, Wesseling, Pieter, Weller, Michael, Collins, Vincent Peter, Blümcke, Ingmar, Bendszus, Martin, Debus, Jürgen, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Robinson, Giles W., Taylor, Michael D., Jaunmuktane, Zane, Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Karajannis, Matthias A., Mittelbronn, Michel, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Schüller, Ulrich, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Brandner, Sebastian, Korshunov, Andrey, Von Deimling, Andreas, Pfister, Stefan M., Capper, David, Jones, David T.W., Sill, Martin, Hovestadt, Volker, Schrimpf, Daniel, Sturm, Dominik, Koelsche, Christian, Sahm, Felix, Chavez, Lukas, Reuss, David E., Kratz, Annekathrin, Wefers, Annika K., Huang, Kristin, Pajtler, Kristian W., Schweizer, Leonille, Stichel, Damian, Olar, Adriana, Engel, Nils W., Lindenberg, Kerstin, Harter, Patrick N., Braczynski, Anne K., Plate, Karl H., Dohmen, Hildegard, Garvalov, Boyan K., Coras, Roland, Hölsken, Annett, Hewer, Ekkehard, Bewerunge-Hudler, Melanie, Schick, Matthias, Fischer, Roger, Beschorner, Rudi, Schittenhelm, Jens, Staszewski, Ori, Wani, Khalida, Varlet, Pascale, Pages, Melanie, Temming, Petra, Lohmann, Dietmar, Selt, Florian, Witt, Hendrik, Milde, Till, Witt, Olaf, Aronica, Eleonora, Giangaspero, Felice, Rushing, Elisabeth, Scheurlen, Wolfram, Geisenberger, Christoph, Rodriguez, Fausto J., Becker, Albert, Preusser, Matthias, Haberler, Christine, Bjerkvig, Rolf, Cryan, Jane, Farrell, Michael, Deckert, Martina, Hench, Jürgen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brück, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Hänggi, Daniel, Hans, Volkmar, Rozsnoki, Stephanie, Hansford, Jordan R., Kohlhof, Patricia, Kristensen, Bjarne W., Lechner, Matt, Lopes, Beatriz, Mawrin, Christian, Ketter, Ralf, Kulozik, Andreas, Khatib, Ziad, Heppner, Frank, Koch, Arend, Jouvet, Anne, Keohane, Catherine, Mühleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G., Driever, Pablo Hernáiz, Kramm, Christof M., Müller, Hermann L., Rutkowski, Stefan, Von Hoff, Katja, Frühwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia Maria, Perry, Arie, Jones, Chris, Jacques, Thomas S., Radlwimmer, Bernhard, Gessi, Marco, Pietsch, Torsten, Schramm, Johannes, Schackert, Gabriele, Westphal, Manfred, Reifenberger, Guido, Wesseling, Pieter, Weller, Michael, Collins, Vincent Peter, Blümcke, Ingmar, Bendszus, Martin, Debus, Jürgen, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Robinson, Giles W., Taylor, Michael D., Jaunmuktane, Zane, Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Karajannis, Matthias A., Mittelbronn, Michel, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Schüller, Ulrich, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Brandner, Sebastian, Korshunov, Andrey, Von Deimling, Andreas, and Pfister, Stefan M.
Published: 2018

25. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort.

Author: Waszak, Sebastian M, Waszak, Sebastian M, Northcott, Paul A, Buchhalter, Ivo, Robinson, Giles W, Sutter, Christian, Groebner, Susanne, Grund, Kerstin B, Brugières, Laurence, Jones, David TW, Pajtler, Kristian W, Morrissy, A Sorana, Kool, Marcel, Sturm, Dominik, Chavez, Lukas, Ernst, Aurelie, Brabetz, Sebastian, Hain, Michael, Zichner, Thomas, Segura-Wang, Maia, Weischenfeldt, Joachim, Rausch, Tobias, Mardin, Balca R, Zhou, Xin, Baciu, Cristina, Lawerenz, Christian, Chan, Jennifer A, Varlet, Pascale, Guerrini-Rousseau, Lea, Fults, Daniel W, Grajkowska, Wiesława, Hauser, Peter, Jabado, Nada, Ra, Young-Shin, Zitterbart, Karel, Shringarpure, Suyash S, De La Vega, Francisco M, Bustamante, Carlos D, Ng, Ho-Keung, Perry, Arie, MacDonald, Tobey J, Hernáiz Driever, Pablo, Bendel, Anne E, Bowers, Daniel C, McCowage, Geoffrey, Chintagumpala, Murali M, Cohn, Richard, Hassall, Timothy, Fleischhack, Gudrun, Eggen, Tone, Wesenberg, Finn, Feychting, Maria, Lannering, Birgitta, Schüz, Joachim, Johansen, Christoffer, Andersen, Tina V, Röösli, Martin, Kuehni, Claudia E, Grotzer, Michael, Kjaerheim, Kristina, Monoranu, Camelia M, Archer, Tenley C, Duke, Elizabeth, Pomeroy, Scott L, Shelagh, Redmond, Frank, Stephan, Sumerauer, David, Scheurlen, Wolfram, Ryzhova, Marina V, Milde, Till, Kratz, Christian P, Samuel, David, Zhang, Jinghui, Solomon, David A, Marra, Marco, Eils, Roland, Bartram, Claus R, von Hoff, Katja, Rutkowski, Stefan, Ramaswamy, Vijay, Gilbertson, Richard J, Korshunov, Andrey, Taylor, Michael D, Lichter, Peter, Malkin, David, Gajjar, Amar, Korbel, Jan O, Pfister, Stefan M, Waszak, Sebastian M, Waszak, Sebastian M, Northcott, Paul A, Buchhalter, Ivo, Robinson, Giles W, Sutter, Christian, Groebner, Susanne, Grund, Kerstin B, Brugières, Laurence, Jones, David TW, Pajtler, Kristian W, Morrissy, A Sorana, Kool, Marcel, Sturm, Dominik, Chavez, Lukas, Ernst, Aurelie, Brabetz, Sebastian, Hain, Michael, Zichner, Thomas, Segura-Wang, Maia, Weischenfeldt, Joachim, Rausch, Tobias, Mardin, Balca R, Zhou, Xin, Baciu, Cristina, Lawerenz, Christian, Chan, Jennifer A, Varlet, Pascale, Guerrini-Rousseau, Lea, Fults, Daniel W, Grajkowska, Wiesława, Hauser, Peter, Jabado, Nada, Ra, Young-Shin, Zitterbart, Karel, Shringarpure, Suyash S, De La Vega, Francisco M, Bustamante, Carlos D, Ng, Ho-Keung, Perry, Arie, MacDonald, Tobey J, Hernáiz Driever, Pablo, Bendel, Anne E, Bowers, Daniel C, McCowage, Geoffrey, Chintagumpala, Murali M, Cohn, Richard, Hassall, Timothy, Fleischhack, Gudrun, Eggen, Tone, Wesenberg, Finn, Feychting, Maria, Lannering, Birgitta, Schüz, Joachim, Johansen, Christoffer, Andersen, Tina V, Röösli, Martin, Kuehni, Claudia E, Grotzer, Michael, Kjaerheim, Kristina, Monoranu, Camelia M, Archer, Tenley C, Duke, Elizabeth, Pomeroy, Scott L, Shelagh, Redmond, Frank, Stephan, Sumerauer, David, Scheurlen, Wolfram, Ryzhova, Marina V, Milde, Till, Kratz, Christian P, Samuel, David, Zhang, Jinghui, Solomon, David A, Marra, Marco, Eils, Roland, Bartram, Claus R, von Hoff, Katja, Rutkowski, Stefan, Ramaswamy, Vijay, Gilbertson, Richard J, Korshunov, Andrey, Taylor, Michael D, Lichter, Peter, Malkin, David, Gajjar, Amar, Korbel, Jan O, and Pfister, Stefan M
Abstract: BackgroundMedulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines.MethodsIn this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma.FindingsWe included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In our rare variant burden analysis, we compared these aga
Published: 2018

26. Proteomics, Post-translational Modifications, and Integrative Analyses Reveal Molecular Heterogeneity within Medulloblastoma Subgroups.

Author: Archer, Tenley C, Archer, Tenley C, Ehrenberger, Tobias, Mundt, Filip, Gold, Maxwell P, Krug, Karsten, Mah, Clarence K, Mahoney, Elizabeth L, Daniel, Colin J, LeNail, Alexander, Ramamoorthy, Divya, Mertins, Philipp, Mani, DR, Zhang, Hailei, Gillette, Michael A, Clauser, Karl, Noble, Michael, Tang, Lauren C, Pierre-François, Jessica, Silterra, Jacob, Jensen, James, Tamayo, Pablo, Korshunov, Andrey, Pfister, Stefan M, Kool, Marcel, Northcott, Paul A, Sears, Rosalie C, Lipton, Jonathan O, Carr, Steven A, Mesirov, Jill P, Pomeroy, Scott L, Fraenkel, Ernest, Archer, Tenley C, Archer, Tenley C, Ehrenberger, Tobias, Mundt, Filip, Gold, Maxwell P, Krug, Karsten, Mah, Clarence K, Mahoney, Elizabeth L, Daniel, Colin J, LeNail, Alexander, Ramamoorthy, Divya, Mertins, Philipp, Mani, DR, Zhang, Hailei, Gillette, Michael A, Clauser, Karl, Noble, Michael, Tang, Lauren C, Pierre-François, Jessica, Silterra, Jacob, Jensen, James, Tamayo, Pablo, Korshunov, Andrey, Pfister, Stefan M, Kool, Marcel, Northcott, Paul A, Sears, Rosalie C, Lipton, Jonathan O, Carr, Steven A, Mesirov, Jill P, Pomeroy, Scott L, and Fraenkel, Ernest
Abstract: There is a pressing need to identify therapeutic targets in tumors with low mutation rates such as the malignant pediatric brain tumor medulloblastoma. To address this challenge, we quantitatively profiled global proteomes and phospho-proteomes of 45 medulloblastoma samples. Integrated analyses revealed that tumors with similar RNA expression vary extensively at the post-transcriptional and post-translational levels. We identified distinct pathways associated with two subsets of SHH tumors, and found post-translational modifications of MYC that are associated with poor outcomes in group 3 tumors. We found kinases associated with subtypes and showed that inhibiting PRKDC sensitizes MYC-driven cells to radiation. Our study shows that proteomics enables a more comprehensive, functional readout, providing a foundation for future therapeutic strategies.
Published: 2018

27. DNA methylation-based classification of central nervous system tumours

Author: Pathologie Pathologen staf, Capper, David, Jones, David T.W., Sill, Martin, Hovestadt, Volker, Schrimpf, Daniel, Sturm, Dominik, Koelsche, Christian, Sahm, Felix, Chavez, Lukas, Reuss, David E., Kratz, Annekathrin, Wefers, Annika K., Huang, Kristin, Pajtler, Kristian W., Schweizer, Leonille, Stichel, Damian, Olar, Adriana, Engel, Nils W., Lindenberg, Kerstin, Harter, Patrick N., Braczynski, Anne K., Plate, Karl H., Dohmen, Hildegard, Garvalov, Boyan K., Coras, Roland, Hölsken, Annett, Hewer, Ekkehard, Bewerunge-Hudler, Melanie, Schick, Matthias, Fischer, Roger, Beschorner, Rudi, Schittenhelm, Jens, Staszewski, Ori, Wani, Khalida, Varlet, Pascale, Pages, Melanie, Temming, Petra, Lohmann, Dietmar, Selt, Florian, Witt, Hendrik, Milde, Till, Witt, Olaf, Aronica, Eleonora, Giangaspero, Felice, Rushing, Elisabeth, Scheurlen, Wolfram, Geisenberger, Christoph, Rodriguez, Fausto J., Becker, Albert, Preusser, Matthias, Haberler, Christine, Bjerkvig, Rolf, Cryan, Jane, Farrell, Michael, Deckert, Martina, Hench, Jürgen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brück, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Hänggi, Daniel, Hans, Volkmar, Rozsnoki, Stephanie, Hansford, Jordan R., Kohlhof, Patricia, Kristensen, Bjarne W., Lechner, Matt, Lopes, Beatriz, Mawrin, Christian, Ketter, Ralf, Kulozik, Andreas, Khatib, Ziad, Heppner, Frank, Koch, Arend, Jouvet, Anne, Keohane, Catherine, Mühleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G., Driever, Pablo Hernáiz, Kramm, Christof M., Müller, Hermann L., Rutkowski, Stefan, Von Hoff, Katja, Frühwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia Maria, Perry, Arie, Jones, Chris, Jacques, Thomas S., Radlwimmer, Bernhard, Gessi, Marco, Pietsch, Torsten, Schramm, Johannes, Schackert, Gabriele, Westphal, Manfred, Reifenberger, Guido, Wesseling, Pieter, Weller, Michael, Collins, Vincent Peter, Blümcke, Ingmar, Bendszus, Martin, Debus, Jürgen, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Robinson, Giles W., Taylor, Michael D., Jaunmuktane, Zane, Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Karajannis, Matthias A., Mittelbronn, Michel, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Schüller, Ulrich, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Brandner, Sebastian, Korshunov, Andrey, Von Deimling, Andreas, Pfister, Stefan M., Pathologie Pathologen staf, Capper, David, Jones, David T.W., Sill, Martin, Hovestadt, Volker, Schrimpf, Daniel, Sturm, Dominik, Koelsche, Christian, Sahm, Felix, Chavez, Lukas, Reuss, David E., Kratz, Annekathrin, Wefers, Annika K., Huang, Kristin, Pajtler, Kristian W., Schweizer, Leonille, Stichel, Damian, Olar, Adriana, Engel, Nils W., Lindenberg, Kerstin, Harter, Patrick N., Braczynski, Anne K., Plate, Karl H., Dohmen, Hildegard, Garvalov, Boyan K., Coras, Roland, Hölsken, Annett, Hewer, Ekkehard, Bewerunge-Hudler, Melanie, Schick, Matthias, Fischer, Roger, Beschorner, Rudi, Schittenhelm, Jens, Staszewski, Ori, Wani, Khalida, Varlet, Pascale, Pages, Melanie, Temming, Petra, Lohmann, Dietmar, Selt, Florian, Witt, Hendrik, Milde, Till, Witt, Olaf, Aronica, Eleonora, Giangaspero, Felice, Rushing, Elisabeth, Scheurlen, Wolfram, Geisenberger, Christoph, Rodriguez, Fausto J., Becker, Albert, Preusser, Matthias, Haberler, Christine, Bjerkvig, Rolf, Cryan, Jane, Farrell, Michael, Deckert, Martina, Hench, Jürgen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brück, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Hänggi, Daniel, Hans, Volkmar, Rozsnoki, Stephanie, Hansford, Jordan R., Kohlhof, Patricia, Kristensen, Bjarne W., Lechner, Matt, Lopes, Beatriz, Mawrin, Christian, Ketter, Ralf, Kulozik, Andreas, Khatib, Ziad, Heppner, Frank, Koch, Arend, Jouvet, Anne, Keohane, Catherine, Mühleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G., Driever, Pablo Hernáiz, Kramm, Christof M., Müller, Hermann L., Rutkowski, Stefan, Von Hoff, Katja, Frühwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia Maria, Perry, Arie, Jones, Chris, Jacques, Thomas S., Radlwimmer, Bernhard, Gessi, Marco, Pietsch, Torsten, Schramm, Johannes, Schackert, Gabriele, Westphal, Manfred, Reifenberger, Guido, Wesseling, Pieter, Weller, Michael, Collins, Vincent Peter, Blümcke, Ingmar, Bendszus, Martin, Debus, Jürgen, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Robinson, Giles W., Taylor, Michael D., Jaunmuktane, Zane, Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Karajannis, Matthias A., Mittelbronn, Michel, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Schüller, Ulrich, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Brandner, Sebastian, Korshunov, Andrey, Von Deimling, Andreas, and Pfister, Stefan M.
Published: 2018

28. The landscape of genomic alterations across childhood cancers

Author: Groebner, Susanne N., Worst, Barbara C., Weischenfeldt, Joachim, Buchhalter, Ivo, Kleinheinz, Kortine, Rudneva, Vasilisa A., Johann, Pascal D., Balasubramanian, Gnana Prakash, Segura-Wang, Maia, Brabetz, Sebastian, Bender, Sebastian, Hutter, Barbara, Sturm, Dominik, Pfaff, Elke, Huebschmann, Daniel, Zipprich, Gideon, Heinold, Michael, Eils, Jurgen, Lawerenz, Christian, Erkek, Serap, Lambo, Sander, Waszak, Sebastian, Blattmann, Claudia, Borkhardt, Arndt, Kuhlen, Michaela, Eggert, Angelika, Fulda, Simone, Gessler, Manfred, Wegert, Jenny, Kappler, Roland, Baumhoer, Daniel, Burdach, Stefan, Kirschner-Schwabe, Renate, Kontny, Udo, Kulozik, Andreas E., Lohmann, Dietmar, Hettmer, Simone, Eckert, Cornelia, Bielack, Stefan, Nathrath, Michaela, Niemeyer, Charlotte, Richter, Gunther H., Schulte, Johannes, Siebert, Reiner, Westermann, Frank, Molenaar, Jan J., Vassal, Gilles, Witt, Hendrik, Burkhardt, Birgit, Kratz, Christian P., Witt, Olaf, van Tilburg, Cornelis M., Kramm, Christof M., Fleischhack, Gudrun, Dirksen, Uta, Rutkowski, Stefan, Fruhwald, Michael, von Hoff, Katja, Wolf, Stephan, Klingebiel, Thomas, Koscielniak, Ewa, Landgraf, Pablo, Koster, Jan, Resnick, Adam C., Zhang, Jinghui, Liu, Yanling, Zhou, Xin, Waanders, Angela J., Zwijnenburg, Danny A., Raman, Pichai, Brors, Benedikt, Weber, Ursula D., Northcott, Paul A., Pajtler, Kristian W., Kool, Marcel, Piro, Rosario M., Korbel, Jan O., Schlesner, Matthias, Eils, Roland, Jones, David T. W., Lichter, Peter, Chavez, Lukas, Zapatka, Marc, Pfister, Stefan M., Groebner, Susanne N., Worst, Barbara C., Weischenfeldt, Joachim, Buchhalter, Ivo, Kleinheinz, Kortine, Rudneva, Vasilisa A., Johann, Pascal D., Balasubramanian, Gnana Prakash, Segura-Wang, Maia, Brabetz, Sebastian, Bender, Sebastian, Hutter, Barbara, Sturm, Dominik, Pfaff, Elke, Huebschmann, Daniel, Zipprich, Gideon, Heinold, Michael, Eils, Jurgen, Lawerenz, Christian, Erkek, Serap, Lambo, Sander, Waszak, Sebastian, Blattmann, Claudia, Borkhardt, Arndt, Kuhlen, Michaela, Eggert, Angelika, Fulda, Simone, Gessler, Manfred, Wegert, Jenny, Kappler, Roland, Baumhoer, Daniel, Burdach, Stefan, Kirschner-Schwabe, Renate, Kontny, Udo, Kulozik, Andreas E., Lohmann, Dietmar, Hettmer, Simone, Eckert, Cornelia, Bielack, Stefan, Nathrath, Michaela, Niemeyer, Charlotte, Richter, Gunther H., Schulte, Johannes, Siebert, Reiner, Westermann, Frank, Molenaar, Jan J., Vassal, Gilles, Witt, Hendrik, Burkhardt, Birgit, Kratz, Christian P., Witt, Olaf, van Tilburg, Cornelis M., Kramm, Christof M., Fleischhack, Gudrun, Dirksen, Uta, Rutkowski, Stefan, Fruhwald, Michael, von Hoff, Katja, Wolf, Stephan, Klingebiel, Thomas, Koscielniak, Ewa, Landgraf, Pablo, Koster, Jan, Resnick, Adam C., Zhang, Jinghui, Liu, Yanling, Zhou, Xin, Waanders, Angela J., Zwijnenburg, Danny A., Raman, Pichai, Brors, Benedikt, Weber, Ursula D., Northcott, Paul A., Pajtler, Kristian W., Kool, Marcel, Piro, Rosario M., Korbel, Jan O., Schlesner, Matthias, Eils, Roland, Jones, David T. W., Lichter, Peter, Chavez, Lukas, Zapatka, Marc, and Pfister, Stefan M.
Abstract: Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7-8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.
Published: 2018

29. DNA methylation-based classification of central nervous system tumours

Author: Capper, David, Jones, David T. W., Sill, Martin, Hovestadt, Volker, Schrimpf, Daniel, Sturm, Dominik, Koelsche, Christian, Sahm, Felix, Chavez, Lukas, Reuss, David E., Kratz, Annekathrin, Wefers, Annika K., Huang, Kristin, Pajtler, Kristian W., Schweizer, Leonille, Stichel, Damian, Olar, Adriana, Engel, Nils W., Lindenberg, Kerstin, Harter, Patrick N., Braczynski, Anne K., Plate, Karl H., Dohmen, Hildegard, Garvalov, Boyan K., Coras, Roland, Hoelsken, Annett, Hewer, Ekkehard, Bewerunge-Hudler, Melanie, Schick, Matthias, Fischer, Roger, Beschorner, Rudi, Schittenhelm, Jens, Staszewski, Ori, Wani, Khalida, Varlet, Pascale, Pages, Melanie, Temming, Petra, Lohmann, Dietmar, Selt, Florian, Witt, Hendrik, Milde, Till, Witt, Olaf, Aronica, Eleonora, Giangaspero, Felice, Rushing, Elisabeth, Scheurlen, Wolfram, Geisenberger, Christoph, Rodriguez, Fausto J., Becker, Albert, Preusser, Matthias, Haberler, Christine, Bjerkvig, Rolf, Cryan, Jane, Farrell, Michael, Deckert, Martina, Hench, Juergen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brueck, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Haenggi, Daniel, Hans, Volkmar, Rozsnoki, Stephanie, Hansford, Jordan R., Kohlhof, Patricia, Kristensen, Bjarne W., Lechner, Matt, Lopes, Beatriz, Mawrin, Christian, Ketter, Ralf, Kulozik, Andreas, Khatib, Ziad, Heppner, Frank, Koch, Arend, Jouvet, Anne, Keohane, Catherine, Muehleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G., Driever, Pablo Hernaiz, Kramm, Christof M., Mueller, Hermann L., Rutkowski, Stefan, von Hoff, Katja, Fruehwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia-Maria, Perry, Arie, Jones, Chris, Jacques, Thomas S., Radlwimmer, Bernhard, Gessi, Marco, Pietsch, Torsten, Schramm, Johannes, Schackert, Gabriele, Westphal, Manfred, Reifenberger, Guido, Wesseling, Pieter, Weller, Michael, Collins, Vincent Peter, Bluemcke, Ingmar, Bendszus, Martin, Debus, Juergen, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Robinson, Giles W., Taylor, Michael D., Jaunmuktane, Zane, Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Karajannis, Matthias A., Mittelbronn, Michel, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Schueller, Ulrich, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Brandner, Sebastian, Korshunov, Andrey, von Deimling, Andreas, Pfister, Stefan M., Capper, David, Jones, David T. W., Sill, Martin, Hovestadt, Volker, Schrimpf, Daniel, Sturm, Dominik, Koelsche, Christian, Sahm, Felix, Chavez, Lukas, Reuss, David E., Kratz, Annekathrin, Wefers, Annika K., Huang, Kristin, Pajtler, Kristian W., Schweizer, Leonille, Stichel, Damian, Olar, Adriana, Engel, Nils W., Lindenberg, Kerstin, Harter, Patrick N., Braczynski, Anne K., Plate, Karl H., Dohmen, Hildegard, Garvalov, Boyan K., Coras, Roland, Hoelsken, Annett, Hewer, Ekkehard, Bewerunge-Hudler, Melanie, Schick, Matthias, Fischer, Roger, Beschorner, Rudi, Schittenhelm, Jens, Staszewski, Ori, Wani, Khalida, Varlet, Pascale, Pages, Melanie, Temming, Petra, Lohmann, Dietmar, Selt, Florian, Witt, Hendrik, Milde, Till, Witt, Olaf, Aronica, Eleonora, Giangaspero, Felice, Rushing, Elisabeth, Scheurlen, Wolfram, Geisenberger, Christoph, Rodriguez, Fausto J., Becker, Albert, Preusser, Matthias, Haberler, Christine, Bjerkvig, Rolf, Cryan, Jane, Farrell, Michael, Deckert, Martina, Hench, Juergen, Frank, Stephan, Serrano, Jonathan, Kannan, Kasthuri, Tsirigos, Aristotelis, Brueck, Wolfgang, Hofer, Silvia, Brehmer, Stefanie, Seiz-Rosenhagen, Marcel, Haenggi, Daniel, Hans, Volkmar, Rozsnoki, Stephanie, Hansford, Jordan R., Kohlhof, Patricia, Kristensen, Bjarne W., Lechner, Matt, Lopes, Beatriz, Mawrin, Christian, Ketter, Ralf, Kulozik, Andreas, Khatib, Ziad, Heppner, Frank, Koch, Arend, Jouvet, Anne, Keohane, Catherine, Muehleisen, Helmut, Mueller, Wolf, Pohl, Ute, Prinz, Marco, Benner, Axel, Zapatka, Marc, Gottardo, Nicholas G., Driever, Pablo Hernaiz, Kramm, Christof M., Mueller, Hermann L., Rutkowski, Stefan, von Hoff, Katja, Fruehwald, Michael C., Gnekow, Astrid, Fleischhack, Gudrun, Tippelt, Stephan, Calaminus, Gabriele, Monoranu, Camelia-Maria, Perry, Arie, Jones, Chris, Jacques, Thomas S., Radlwimmer, Bernhard, Gessi, Marco, Pietsch, Torsten, Schramm, Johannes, Schackert, Gabriele, Westphal, Manfred, Reifenberger, Guido, Wesseling, Pieter, Weller, Michael, Collins, Vincent Peter, Bluemcke, Ingmar, Bendszus, Martin, Debus, Juergen, Huang, Annie, Jabado, Nada, Northcott, Paul A., Paulus, Werner, Gajjar, Amar, Robinson, Giles W., Taylor, Michael D., Jaunmuktane, Zane, Ryzhova, Marina, Platten, Michael, Unterberg, Andreas, Wick, Wolfgang, Karajannis, Matthias A., Mittelbronn, Michel, Acker, Till, Hartmann, Christian, Aldape, Kenneth, Schueller, Ulrich, Buslei, Rolf, Lichter, Peter, Kool, Marcel, Herold-Mende, Christel, Ellison, David W., Hasselblatt, Martin, Snuderl, Matija, Brandner, Sebastian, Korshunov, Andrey, von Deimling, Andreas, and Pfister, Stefan M.
Abstract: Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challengingwith substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.
Published: 2018

30. Spectrum and prevalence of genetic predisposition in medulloblastoma:a retrospective genetic study and prospective validation in a clinical trial cohort

Author: Waszak, Sebastian M., Northcott, Paul A., Buchhalter, Ivo, Robinson, Giles W., Sutter, Christian, Groebner, Susanne, Grund, Kerstin B., Brugières, Laurence, Jones, David T.W., Pajtler, Kristian W., Morrissy, A. Sorana, Kool, Marcel, Sturm, Dominik, Chavez, Lukas, Ernst, Aurelie, Brabetz, Sebastian, Hain, Michael, Zichner, Thomas, Segura-Wang, Maia, Weischenfeldt, Joachim, Rausch, Tobias, Mardin, Balca R., Zhou, Xin, Baciu, Cristina, Lawerenz, Christian, Chan, Jennifer A., Varlet, Pascale, Guerrini-Rousseau, Lea, Fults, Daniel W., Grajkowska, Wiesława, Hauser, Peter, Jabado, Nada, Ra, Young Shin, Zitterbart, Karel, Shringarpure, Suyash S., De La Vega, Francisco M., Bustamante, Carlos D., Ng, Ho Keung, Perry, Arie, MacDonald, Tobey J., Hernáiz Driever, Pablo, Bendel, Anne E., Bowers, Daniel C., McCowage, Geoffrey, Chintagumpala, Murali M., Cohn, Richard, Hassall, Timothy, Fleischhack, Gudrun, Eggen, Tone, Wesenberg, Finn, Feychting, Maria, Lannering, Birgitta, Schüz, Joachim, Johansen, Christoffer, Andersen, Tina V., Röösli, Martin, Kuehni, Claudia E., Grotzer, Michael, Kjaerheim, Kristina, Monoranu, Camelia M., Archer, Tenley C., Duke, Elizabeth, Pomeroy, Scott L., Shelagh, Redmond, Frank, Stephan, Sumerauer, David, Scheurlen, Wolfram, Ryzhova, Marina V., Milde, Till, Kratz, Christian P., Samuel, David, Zhang, Jinghui, Solomon, David A., Marra, Marco, Eils, Roland, Bartram, Claus R., von Hoff, Katja, Rutkowski, Stefan, Ramaswamy, Vijay, Gilbertson, Richard J., Korshunov, Andrey, Taylor, Michael D., Lichter, Peter, Malkin, David, Gajjar, Amar, Korbel, Jan O., Pfister, Stefan M., Waszak, Sebastian M., Northcott, Paul A., Buchhalter, Ivo, Robinson, Giles W., Sutter, Christian, Groebner, Susanne, Grund, Kerstin B., Brugières, Laurence, Jones, David T.W., Pajtler, Kristian W., Morrissy, A. Sorana, Kool, Marcel, Sturm, Dominik, Chavez, Lukas, Ernst, Aurelie, Brabetz, Sebastian, Hain, Michael, Zichner, Thomas, Segura-Wang, Maia, Weischenfeldt, Joachim, Rausch, Tobias, Mardin, Balca R., Zhou, Xin, Baciu, Cristina, Lawerenz, Christian, Chan, Jennifer A., Varlet, Pascale, Guerrini-Rousseau, Lea, Fults, Daniel W., Grajkowska, Wiesława, Hauser, Peter, Jabado, Nada, Ra, Young Shin, Zitterbart, Karel, Shringarpure, Suyash S., De La Vega, Francisco M., Bustamante, Carlos D., Ng, Ho Keung, Perry, Arie, MacDonald, Tobey J., Hernáiz Driever, Pablo, Bendel, Anne E., Bowers, Daniel C., McCowage, Geoffrey, Chintagumpala, Murali M., Cohn, Richard, Hassall, Timothy, Fleischhack, Gudrun, Eggen, Tone, Wesenberg, Finn, Feychting, Maria, Lannering, Birgitta, Schüz, Joachim, Johansen, Christoffer, Andersen, Tina V., Röösli, Martin, Kuehni, Claudia E., Grotzer, Michael, Kjaerheim, Kristina, Monoranu, Camelia M., Archer, Tenley C., Duke, Elizabeth, Pomeroy, Scott L., Shelagh, Redmond, Frank, Stephan, Sumerauer, David, Scheurlen, Wolfram, Ryzhova, Marina V., Milde, Till, Kratz, Christian P., Samuel, David, Zhang, Jinghui, Solomon, David A., Marra, Marco, Eils, Roland, Bartram, Claus R., von Hoff, Katja, Rutkowski, Stefan, Ramaswamy, Vijay, Gilbertson, Richard J., Korshunov, Andrey, Taylor, Michael D., Lichter, Peter, Malkin, David, Gajjar, Amar, Korbel, Jan O., and Pfister, Stefan M.
Abstract: Background: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In
Published: 2018

31. UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs

Author: European Commission, Cancer Research UK, Medical Research Council (UK), Wellcome Trust Centre for Human Genetics, CRUK Cambridge Centre, Kay Kendall Leukaemia Fund, Wellcome Sanger Institute, Gozdecka, Malgorzata, Meduri, Eshwar, Mazan, Milena, Tzelepis, Konstantinos, Dudek, Monika, Knights, Andrew J., Pardo, Mercedes, Yu, Lu, Choudhary, Jyoti S., Metzakopian, Emmanouil, Iyer, Vivek, Yun, Haiyang, Park, Naomi, Varela, Ignacio, Bautista, Rubén, Collord, Grace, Dovey, Oliver M., Garyfallos, Dimitrios A., Braekeleer, Etienne De, Kondo, Saki, Cooper, Jonathan, Göttgens, Berthold, Bullinger, Lars, Northcott, Paul A., Adams, David, Vassiliou, George S., Huntly, Brian J. P., European Commission, Cancer Research UK, Medical Research Council (UK), Wellcome Trust Centre for Human Genetics, CRUK Cambridge Centre, Kay Kendall Leukaemia Fund, Wellcome Sanger Institute, Gozdecka, Malgorzata, Meduri, Eshwar, Mazan, Milena, Tzelepis, Konstantinos, Dudek, Monika, Knights, Andrew J., Pardo, Mercedes, Yu, Lu, Choudhary, Jyoti S., Metzakopian, Emmanouil, Iyer, Vivek, Yun, Haiyang, Park, Naomi, Varela, Ignacio, Bautista, Rubén, Collord, Grace, Dovey, Oliver M., Garyfallos, Dimitrios A., Braekeleer, Etienne De, Kondo, Saki, Cooper, Jonathan, Göttgens, Berthold, Bullinger, Lars, Northcott, Paul A., Adams, David, Vassiliou, George S., and Huntly, Brian J. P.
Abstract: The histone H3 Lys27-specific demethylase UTX (or KDM6A) is targeted by loss-of-function mutations in multiple cancers. Here, we demonstrate that UTX suppresses myeloid leukemogenesis through noncatalytic functions, a property shared with its catalytically inactive Y-chromosome paralog, UTY (or KDM6C). In keeping with this, we demonstrate concomitant loss/mutation of KDM6A (UTX) and UTY in multiple human cancers. Mechanistically, global genomic profiling showed only minor changes in H3K27me3 but significant and bidirectional alterations in H3K27ac and chromatin accessibility; a predominant loss of H3K4me1 modifications; alterations in ETS and GATA-factor binding; and altered gene expression after Utx loss. By integrating proteomic and genomic analyses, we link these changes to UTX regulation of ATP-dependent chromatin remodeling, coordination of the COMPASS complex and enhanced pioneering activity of ETS factors during evolution to AML. Collectively, our findings identify a dual role for UTX in suppressing acute myeloid leukemia via repression of oncogenic ETS and upregulation of tumor-suppressive GATA programs.
Published: 2018

32. The whole-genome landscape of medulloblastoma subtypes

Author: Massachusetts Institute of Technology. Department of Biological Engineering, Ehrenberger, Tobias, Fraenkel, Ernest, Northcott, Paul A., Buchhalter, Ivo, Morrissy, A. Sorana, Hovestadt, Volker, Weischenfeldt, Joachim, Gröbner, Susanne, Segura-Wang, Maia, Zichner, Thomas, Rudneva, Vasilisa A., Warnatz, Hans-Jörg, Sidiropoulos, Nikos, Phillips, Aaron H., Schumacher, Steven, Kleinheinz, Kortine, Waszak, Sebastian M., Erkek, Serap, Jones, David T. W., Worst, Barbara C., Kool, Marcel, Zapatka, Marc, Jäger, Natalie, Chavez, Lukas, Hutter, Barbara, Bieg, Matthias, Paramasivam, Nagarajan, Heinold, Michael, Gu, Zuguang, Ishaque, Naveed, Jäger-Schmidt, Christina, Imbusch, Charles D., Jugold, Alke, Hübschmann, Daniel, Risch, Thomas, Amstislavskiy, Vyacheslav, Gonzalez, Francisco German Rodriguez, Weber, Ursula D., Wolf, Stephan, Robinson, Giles W., Zhou, Xin, Wu, Gang, Finkelstein, David, Liu, Yanling, Cavalli, Florence M. G., Luu, Betty, Ramaswamy, Vijay, Wu, Xiaochong, Koster, Jan, Ryzhova, Marina, Cho, Yoon-Jae, Pomeroy, Scott L., Herold-Mende, Christel, Schuhmann, Martin, Ebinger, Martin, Liau, Linda M., Mora, Jaume, McLendon, Roger E., Jabado, Nada, Kumabe, Toshihiro, Chuah, Eric, Ma, Yussanne, Moore, Richard A., Mungall, Andrew J., Mungall, Karen L., Thiessen, Nina, Tse, Kane, Wong, Tina, Jones, Steven J. M., Witt, Olaf, Milde, Till, Von Deimling, Andreas, Capper, David, Korshunov, Andrey, Yaspo, Marie-Laure, Kriwacki, Richard, Gajjar, Amar, Zhang, Jinghui, Beroukhim, Rameen, Korbel, Jan O., Brors, Benedikt, Schlesner, Matthias, Eils, Roland, Marra, Marco A., Pfister, Stefan M., Taylor, Michael D., Lichter, Peter, Massachusetts Institute of Technology. Department of Biological Engineering, Ehrenberger, Tobias, Fraenkel, Ernest, Northcott, Paul A., Buchhalter, Ivo, Morrissy, A. Sorana, Hovestadt, Volker, Weischenfeldt, Joachim, Gröbner, Susanne, Segura-Wang, Maia, Zichner, Thomas, Rudneva, Vasilisa A., Warnatz, Hans-Jörg, Sidiropoulos, Nikos, Phillips, Aaron H., Schumacher, Steven, Kleinheinz, Kortine, Waszak, Sebastian M., Erkek, Serap, Jones, David T. W., Worst, Barbara C., Kool, Marcel, Zapatka, Marc, Jäger, Natalie, Chavez, Lukas, Hutter, Barbara, Bieg, Matthias, Paramasivam, Nagarajan, Heinold, Michael, Gu, Zuguang, Ishaque, Naveed, Jäger-Schmidt, Christina, Imbusch, Charles D., Jugold, Alke, Hübschmann, Daniel, Risch, Thomas, Amstislavskiy, Vyacheslav, Gonzalez, Francisco German Rodriguez, Weber, Ursula D., Wolf, Stephan, Robinson, Giles W., Zhou, Xin, Wu, Gang, Finkelstein, David, Liu, Yanling, Cavalli, Florence M. G., Luu, Betty, Ramaswamy, Vijay, Wu, Xiaochong, Koster, Jan, Ryzhova, Marina, Cho, Yoon-Jae, Pomeroy, Scott L., Herold-Mende, Christel, Schuhmann, Martin, Ebinger, Martin, Liau, Linda M., Mora, Jaume, McLendon, Roger E., Jabado, Nada, Kumabe, Toshihiro, Chuah, Eric, Ma, Yussanne, Moore, Richard A., Mungall, Andrew J., Mungall, Karen L., Thiessen, Nina, Tse, Kane, Wong, Tina, Jones, Steven J. M., Witt, Olaf, Milde, Till, Von Deimling, Andreas, Capper, David, Korshunov, Andrey, Yaspo, Marie-Laure, Kriwacki, Richard, Gajjar, Amar, Zhang, Jinghui, Beroukhim, Rameen, Korbel, Jan O., Brors, Benedikt, Schlesner, Matthias, Eils, Roland, Marra, Marco A., Pfister, Stefan M., Taylor, Michael D., and Lichter, Peter
Abstract: Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.
Published: 2018

33. Spectrum and prevalence of genetic predisposition in medulloblastoma:a retrospective genetic study and prospective validation in a clinical trial cohort

Author: Waszak, Sebastian M., Northcott, Paul A., Buchhalter, Ivo, Robinson, Giles W., Sutter, Christian, Groebner, Susanne, Grund, Kerstin B., Brugières, Laurence, Jones, David T.W., Pajtler, Kristian W., Morrissy, A. Sorana, Kool, Marcel, Sturm, Dominik, Chavez, Lukas, Ernst, Aurelie, Brabetz, Sebastian, Hain, Michael, Zichner, Thomas, Segura-Wang, Maia, Weischenfeldt, Joachim, Rausch, Tobias, Mardin, Balca R., Zhou, Xin, Baciu, Cristina, Lawerenz, Christian, Chan, Jennifer A., Varlet, Pascale, Guerrini-Rousseau, Lea, Fults, Daniel W., Grajkowska, Wiesława, Hauser, Peter, Jabado, Nada, Ra, Young Shin, Zitterbart, Karel, Shringarpure, Suyash S., De La Vega, Francisco M., Bustamante, Carlos D., Ng, Ho Keung, Perry, Arie, MacDonald, Tobey J., Hernáiz Driever, Pablo, Bendel, Anne E., Bowers, Daniel C., McCowage, Geoffrey, Chintagumpala, Murali M., Cohn, Richard, Hassall, Timothy, Fleischhack, Gudrun, Eggen, Tone, Wesenberg, Finn, Feychting, Maria, Lannering, Birgitta, Schüz, Joachim, Johansen, Christoffer, Andersen, Tina V., Röösli, Martin, Kuehni, Claudia E., Grotzer, Michael, Kjaerheim, Kristina, Monoranu, Camelia M., Archer, Tenley C., Duke, Elizabeth, Pomeroy, Scott L., Shelagh, Redmond, Frank, Stephan, Sumerauer, David, Scheurlen, Wolfram, Ryzhova, Marina V., Milde, Till, Kratz, Christian P., Samuel, David, Zhang, Jinghui, Solomon, David A., Marra, Marco, Eils, Roland, Bartram, Claus R., von Hoff, Katja, Rutkowski, Stefan, Ramaswamy, Vijay, Gilbertson, Richard J., Korshunov, Andrey, Taylor, Michael D., Lichter, Peter, Malkin, David, Gajjar, Amar, Korbel, Jan O., Pfister, Stefan M., Waszak, Sebastian M., Northcott, Paul A., Buchhalter, Ivo, Robinson, Giles W., Sutter, Christian, Groebner, Susanne, Grund, Kerstin B., Brugières, Laurence, Jones, David T.W., Pajtler, Kristian W., Morrissy, A. Sorana, Kool, Marcel, Sturm, Dominik, Chavez, Lukas, Ernst, Aurelie, Brabetz, Sebastian, Hain, Michael, Zichner, Thomas, Segura-Wang, Maia, Weischenfeldt, Joachim, Rausch, Tobias, Mardin, Balca R., Zhou, Xin, Baciu, Cristina, Lawerenz, Christian, Chan, Jennifer A., Varlet, Pascale, Guerrini-Rousseau, Lea, Fults, Daniel W., Grajkowska, Wiesława, Hauser, Peter, Jabado, Nada, Ra, Young Shin, Zitterbart, Karel, Shringarpure, Suyash S., De La Vega, Francisco M., Bustamante, Carlos D., Ng, Ho Keung, Perry, Arie, MacDonald, Tobey J., Hernáiz Driever, Pablo, Bendel, Anne E., Bowers, Daniel C., McCowage, Geoffrey, Chintagumpala, Murali M., Cohn, Richard, Hassall, Timothy, Fleischhack, Gudrun, Eggen, Tone, Wesenberg, Finn, Feychting, Maria, Lannering, Birgitta, Schüz, Joachim, Johansen, Christoffer, Andersen, Tina V., Röösli, Martin, Kuehni, Claudia E., Grotzer, Michael, Kjaerheim, Kristina, Monoranu, Camelia M., Archer, Tenley C., Duke, Elizabeth, Pomeroy, Scott L., Shelagh, Redmond, Frank, Stephan, Sumerauer, David, Scheurlen, Wolfram, Ryzhova, Marina V., Milde, Till, Kratz, Christian P., Samuel, David, Zhang, Jinghui, Solomon, David A., Marra, Marco, Eils, Roland, Bartram, Claus R., von Hoff, Katja, Rutkowski, Stefan, Ramaswamy, Vijay, Gilbertson, Richard J., Korshunov, Andrey, Taylor, Michael D., Lichter, Peter, Malkin, David, Gajjar, Amar, Korbel, Jan O., and Pfister, Stefan M.
Abstract: Background: Medulloblastoma is associated with rare hereditary cancer predisposition syndromes; however, consensus medulloblastoma predisposition genes have not been defined and screening guidelines for genetic counselling and testing for paediatric patients are not available. We aimed to assess and define these genes to provide evidence for future screening guidelines. Methods: In this international, multicentre study, we analysed patients with medulloblastoma from retrospective cohorts (International Cancer Genome Consortium [ICGC] PedBrain, Medulloblastoma Advanced Genomics International Consortium [MAGIC], and the CEFALO series) and from prospective cohorts from four clinical studies (SJMB03, SJMB12, SJYC07, and I-HIT-MED). Whole-genome sequences and exome sequences from blood and tumour samples were analysed for rare damaging germline mutations in cancer predisposition genes. DNA methylation profiling was done to determine consensus molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGroup3), and group 4 (MBGroup4). Medulloblastoma predisposition genes were predicted on the basis of rare variant burden tests against controls without a cancer diagnosis from the Exome Aggregation Consortium (ExAC). Previously defined somatic mutational signatures were used to further classify medulloblastoma genomes into two groups, a clock-like group (signatures 1 and 5) and a homologous recombination repair deficiency-like group (signatures 3 and 8), and chromothripsis was investigated using previously established criteria. Progression-free survival and overall survival were modelled for patients with a genetic predisposition to medulloblastoma. Findings: We included a total of 1022 patients with medulloblastoma from the retrospective cohorts (n=673) and the four prospective studies (n=349), from whom blood samples (n=1022) and tumour samples (n=800) were analysed for germline mutations in 110 cancer predisposition genes. In
Published: 2018

34. Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking

Author: Weischenfeldt, Joachim, Dubash, Taronish, Drainas, Alexandros P., Mardin, Balca R., Chen, Yuanyuan, Stuetz, Adrian M., Waszak, Sebastian M., Bosco, Graziella, Halvorsen, Ann Rita, Raeder, Benjamin, Efthymiopoulos, Theocharis, Erkek, Serap, Siegl, Christine, Brenner, Hermann, Brustugun, Odd Terje, Dieter, Sebastian M., Northcott, Paul A., Petersen, Iver, Pfister, Stefan M., Schneider, Martin, Solberg, Steinar K., Thunissen, Erik, Weichert, Wilko, Zichner, Thomas, Thomas, Roman, Peifer, Martin, Helland, Aslaug, Ball, Claudia R., Jechlinger, Martin, Sotillo, Rocio, Glimm, Hanno, Korbel, Jan O., Weischenfeldt, Joachim, Dubash, Taronish, Drainas, Alexandros P., Mardin, Balca R., Chen, Yuanyuan, Stuetz, Adrian M., Waszak, Sebastian M., Bosco, Graziella, Halvorsen, Ann Rita, Raeder, Benjamin, Efthymiopoulos, Theocharis, Erkek, Serap, Siegl, Christine, Brenner, Hermann, Brustugun, Odd Terje, Dieter, Sebastian M., Northcott, Paul A., Petersen, Iver, Pfister, Stefan M., Schneider, Martin, Solberg, Steinar K., Thunissen, Erik, Weichert, Wilko, Zichner, Thomas, Thomas, Roman, Peifer, Martin, Helland, Aslaug, Ball, Claudia R., Jechlinger, Martin, Sotillo, Rocio, Glimm, Hanno, and Korbel, Jan O.
Abstract: Extensive prior research focused on somatic copy-number alterations (SCNAs) affecting cancer genes, yet the extent to which recurrent SCNAs exert their influence through rearrangement of cis-regulatory elements (CREs) remains unclear. Here we present a framework for inferring cancer-related gene overexpression resulting from CRE reorganization (e.g., enhancer hijacking) by integrating SCNAs, gene expression data and information on topologically associating domains (TADS). Analysis of 7,416 cancer genomes uncovered several pan-cancer candidate genes, including IRS4, SMARCA1 and TERT. We demonstrate that IRS4 overexpression in lung cancer is associated with recurrent deletions in cis, and we present evidence supporting a tumor promoting role. We additionally pursued cancer-type-specific analyses and uncovered IGF2 as a target for enhancer hijacking in colorectal cancer. Recurrent tandem duplications intersecting with a TAD boundary mediate de novo formation of a 3D contact domain comprising IGF2 and a lineage-specific super-enhancer, resulting in high-level gene activation. Our framework enables systematic inference of CRE rearrangements mediating dysregulation in cancer.
Published: 2017

35. Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking

Author: Weischenfeldt, Joachim, Dubash, Taronish, Drainas, Alexandros P., Mardin, Balca R., Chen, Yuanyuan, Stuetz, Adrian M., Waszak, Sebastian M., Bosco, Graziella, Halvorsen, Ann Rita, Raeder, Benjamin, Efthymiopoulos, Theocharis, Erkek, Serap, Siegl, Christine, Brenner, Hermann, Brustugun, Odd Terje, Dieter, Sebastian M., Northcott, Paul A., Petersen, Iver, Pfister, Stefan M., Schneider, Martin, Solberg, Steinar K., Thunissen, Erik, Weichert, Wilko, Zichner, Thomas, Thomas, Roman, Peifer, Martin, Helland, Aslaug, Ball, Claudia R., Jechlinger, Martin, Sotillo, Rocio, Glimm, Hanno, Korbel, Jan O., Weischenfeldt, Joachim, Dubash, Taronish, Drainas, Alexandros P., Mardin, Balca R., Chen, Yuanyuan, Stuetz, Adrian M., Waszak, Sebastian M., Bosco, Graziella, Halvorsen, Ann Rita, Raeder, Benjamin, Efthymiopoulos, Theocharis, Erkek, Serap, Siegl, Christine, Brenner, Hermann, Brustugun, Odd Terje, Dieter, Sebastian M., Northcott, Paul A., Petersen, Iver, Pfister, Stefan M., Schneider, Martin, Solberg, Steinar K., Thunissen, Erik, Weichert, Wilko, Zichner, Thomas, Thomas, Roman, Peifer, Martin, Helland, Aslaug, Ball, Claudia R., Jechlinger, Martin, Sotillo, Rocio, Glimm, Hanno, and Korbel, Jan O.
Abstract: Extensive prior research focused on somatic copy-number alterations (SCNAs) affecting cancer genes, yet the extent to which recurrent SCNAs exert their influence through rearrangement of cis-regulatory elements (CREs) remains unclear. Here we present a framework for inferring cancer-related gene overexpression resulting from CRE reorganization (e.g., enhancer hijacking) by integrating SCNAs, gene expression data and information on topologically associating domains (TADS). Analysis of 7,416 cancer genomes uncovered several pan-cancer candidate genes, including IRS4, SMARCA1 and TERT. We demonstrate that IRS4 overexpression in lung cancer is associated with recurrent deletions in cis, and we present evidence supporting a tumor promoting role. We additionally pursued cancer-type-specific analyses and uncovered IGF2 as a target for enhancer hijacking in colorectal cancer. Recurrent tandem duplications intersecting with a TAD boundary mediate de novo formation of a 3D contact domain comprising IGF2 and a lineage-specific super-enhancer, resulting in high-level gene activation. Our framework enables systematic inference of CRE rearrangements mediating dysregulation in cancer.
Published: 2017

36. The whole-genome landscape of medulloblastoma subtypes

Author: Northcott, Paul A., Buchhalter, Ivo, Morrissy, A. Sorana, Hovestadt, Volker, Weischenfeldt, Joachim, Ehrenberger, Tobias, Gröbner, Susanne, Segura-Wang, Maia, Zichner, Thomas, Rudneva, Vasilisa A., Warnatz, Hans Jörg, Sidiropoulos, Nikos, Phillips, Aaron H., Schumacher, Steven, Kleinheinz, Kortine, Waszak, Sebastian M., Erkek, Serap, Jones, David T.W., Worst, Barbara C., Kool, Marcel, Zapatka, Marc, Jäger, Natalie, Chavez, Lukas, Hutter, Barbara, Bieg, Matthias, Paramasivam, Nagarajan, Heinold, Michael, Gu, Zuguang, Ishaque, Naveed, Jäger-Schmidt, Christina, Imbusch, Charles D., Jugold, Alke, Hübschmann, Daniel, Risch, Thomas, Amstislavskiy, Vyacheslav, Gonzalez, Francisco German Rodriguez, Weber, Ursula D., Wolf, Stephan, Robinson, Giles W., Zhou, Xin, Wu, Gang, Finkelstein, David, Liu, Yanling, Cavalli, Florence M.G., Luu, Betty, Ramaswamy, Vijay, Wu, Xiaochong, Koster, Jan, Ryzhova, Marina, Cho, Yoon Jae, Pomeroy, Scott L., Herold-Mende, Christel, Schuhmann, Martin, Ebinger, Martin, Liau, Linda M., Mora, Jaume, McLendon, Roger E., Jabado, Nada, Kumabe, Toshihiro, Chuah, Eric, Ma, Yussanne, Moore, Richard A., Mungall, Andrew J., Mungall, Karen L., Thiessen, Nina, Tse, Kane, Wong, Tina, Jones, Steven J.M., Witt, Olaf, Milde, Till, Von Deimling, Andreas, Capper, David, Korshunov, Andrey, Yaspo, Marie Laure, Kriwacki, Richard, Gajjar, Amar, Zhang, Jinghui, Beroukhim, Rameen, Fraenkel, Ernest, Korbel, Jan O., Brors, Benedikt, Schlesner, Matthias, Eils, Roland, Marra, Marco A., Pfister, Stefan M., Taylor, Michael D., Lichter, Peter, Northcott, Paul A., Buchhalter, Ivo, Morrissy, A. Sorana, Hovestadt, Volker, Weischenfeldt, Joachim, Ehrenberger, Tobias, Gröbner, Susanne, Segura-Wang, Maia, Zichner, Thomas, Rudneva, Vasilisa A., Warnatz, Hans Jörg, Sidiropoulos, Nikos, Phillips, Aaron H., Schumacher, Steven, Kleinheinz, Kortine, Waszak, Sebastian M., Erkek, Serap, Jones, David T.W., Worst, Barbara C., Kool, Marcel, Zapatka, Marc, Jäger, Natalie, Chavez, Lukas, Hutter, Barbara, Bieg, Matthias, Paramasivam, Nagarajan, Heinold, Michael, Gu, Zuguang, Ishaque, Naveed, Jäger-Schmidt, Christina, Imbusch, Charles D., Jugold, Alke, Hübschmann, Daniel, Risch, Thomas, Amstislavskiy, Vyacheslav, Gonzalez, Francisco German Rodriguez, Weber, Ursula D., Wolf, Stephan, Robinson, Giles W., Zhou, Xin, Wu, Gang, Finkelstein, David, Liu, Yanling, Cavalli, Florence M.G., Luu, Betty, Ramaswamy, Vijay, Wu, Xiaochong, Koster, Jan, Ryzhova, Marina, Cho, Yoon Jae, Pomeroy, Scott L., Herold-Mende, Christel, Schuhmann, Martin, Ebinger, Martin, Liau, Linda M., Mora, Jaume, McLendon, Roger E., Jabado, Nada, Kumabe, Toshihiro, Chuah, Eric, Ma, Yussanne, Moore, Richard A., Mungall, Andrew J., Mungall, Karen L., Thiessen, Nina, Tse, Kane, Wong, Tina, Jones, Steven J.M., Witt, Olaf, Milde, Till, Von Deimling, Andreas, Capper, David, Korshunov, Andrey, Yaspo, Marie Laure, Kriwacki, Richard, Gajjar, Amar, Zhang, Jinghui, Beroukhim, Rameen, Fraenkel, Ernest, Korbel, Jan O., Brors, Benedikt, Schlesner, Matthias, Eils, Roland, Marra, Marco A., Pfister, Stefan M., Taylor, Michael D., and Lichter, Peter
Abstract: Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.
Published: 2017

37. Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking

Author: Weischenfeldt, Joachim Lütken, Dubash, Taronish, Drainas, Alexandros P, Mardin, Balca R, Chen, Yuanyuan, Stütz, Adrian M, Waszak, Sebastian M, Bosco, Graziella, Halvorsen, Ann Rita, Raeder, Benjamin, Efthymiopoulos, Theocharis, Erkek, Serap, Siegl, Christine, Brenner, Hermann, Brustugun, Odd Terje, Dieter, Sebastian M, Northcott, Paul A, Petersen, Iver, Pfister, Stefan M, Schneider, Martin, Solberg, Steinar K, Thunissen, Erik, Weichert, Wilko, Zichner, Thomas, Thomas, Roman, Peifer, Martin, Helland, Aslaug, Ball, Claudia R, Jechlinger, Martin, Sotillo, Rocio, Glimm, Hanno, Korbel, Jan O, Weischenfeldt, Joachim Lütken, Dubash, Taronish, Drainas, Alexandros P, Mardin, Balca R, Chen, Yuanyuan, Stütz, Adrian M, Waszak, Sebastian M, Bosco, Graziella, Halvorsen, Ann Rita, Raeder, Benjamin, Efthymiopoulos, Theocharis, Erkek, Serap, Siegl, Christine, Brenner, Hermann, Brustugun, Odd Terje, Dieter, Sebastian M, Northcott, Paul A, Petersen, Iver, Pfister, Stefan M, Schneider, Martin, Solberg, Steinar K, Thunissen, Erik, Weichert, Wilko, Zichner, Thomas, Thomas, Roman, Peifer, Martin, Helland, Aslaug, Ball, Claudia R, Jechlinger, Martin, Sotillo, Rocio, Glimm, Hanno, and Korbel, Jan O
Abstract: Extensive prior research focused on somatic copy-number alterations (SCNAs) affecting cancer genes, yet the extent to which recurrent SCNAs exert their influence through rearrangement of cis-regulatory elements (CREs) remains unclear. Here we present a framework for inferring cancer-related gene overexpression resulting from CRE reorganization (e.g., enhancer hijacking) by integrating SCNAs, gene expression data and information on topologically associating domains (TADs). Analysis of 7,416 cancer genomes uncovered several pan-cancer candidate genes, including IRS4, SMARCA1 and TERT. We demonstrate that IRS4 overexpression in lung cancer is associated with recurrent deletions in cis, and we present evidence supporting a tumor-promoting role. We additionally pursued cancer-type-specific analyses and uncovered IGF2 as a target for enhancer hijacking in colorectal cancer. Recurrent tandem duplications intersecting with a TAD boundary mediate de novo formation of a 3D contact domain comprising IGF2 and a lineage-specific super-enhancer, resulting in high-level gene activation. Our framework enables systematic inference of CRE rearrangements mediating dysregulation in cancer.
Published: 2017

38. The whole-genome landscape of medulloblastoma subtypes

Author: Northcott, Paul A., Buchhalter, Ivo, Morrissy, A. Sorana, Hovestadt, Volker, Weischenfeldt, Joachim, Ehrenberger, Tobias, Gröbner, Susanne, Segura-Wang, Maia, Zichner, Thomas, Rudneva, Vasilisa A., Warnatz, Hans Jörg, Sidiropoulos, Nikos, Phillips, Aaron H., Schumacher, Steven, Kleinheinz, Kortine, Waszak, Sebastian M., Erkek, Serap, Jones, David T.W., Worst, Barbara C., Kool, Marcel, Zapatka, Marc, Jäger, Natalie, Chavez, Lukas, Hutter, Barbara, Bieg, Matthias, Paramasivam, Nagarajan, Heinold, Michael, Gu, Zuguang, Ishaque, Naveed, Jäger-Schmidt, Christina, Imbusch, Charles D., Jugold, Alke, Hübschmann, Daniel, Risch, Thomas, Amstislavskiy, Vyacheslav, Gonzalez, Francisco German Rodriguez, Weber, Ursula D., Wolf, Stephan, Robinson, Giles W., Zhou, Xin, Wu, Gang, Finkelstein, David, Liu, Yanling, Cavalli, Florence M.G., Luu, Betty, Ramaswamy, Vijay, Wu, Xiaochong, Koster, Jan, Ryzhova, Marina, Cho, Yoon Jae, Pomeroy, Scott L., Herold-Mende, Christel, Schuhmann, Martin, Ebinger, Martin, Liau, Linda M., Mora, Jaume, McLendon, Roger E., Jabado, Nada, Kumabe, Toshihiro, Chuah, Eric, Ma, Yussanne, Moore, Richard A., Mungall, Andrew J., Mungall, Karen L., Thiessen, Nina, Tse, Kane, Wong, Tina, Jones, Steven J.M., Witt, Olaf, Milde, Till, Von Deimling, Andreas, Capper, David, Korshunov, Andrey, Yaspo, Marie Laure, Kriwacki, Richard, Gajjar, Amar, Zhang, Jinghui, Beroukhim, Rameen, Fraenkel, Ernest, Korbel, Jan O., Brors, Benedikt, Schlesner, Matthias, Eils, Roland, Marra, Marco A., Pfister, Stefan M., Taylor, Michael D., Lichter, Peter, Northcott, Paul A., Buchhalter, Ivo, Morrissy, A. Sorana, Hovestadt, Volker, Weischenfeldt, Joachim, Ehrenberger, Tobias, Gröbner, Susanne, Segura-Wang, Maia, Zichner, Thomas, Rudneva, Vasilisa A., Warnatz, Hans Jörg, Sidiropoulos, Nikos, Phillips, Aaron H., Schumacher, Steven, Kleinheinz, Kortine, Waszak, Sebastian M., Erkek, Serap, Jones, David T.W., Worst, Barbara C., Kool, Marcel, Zapatka, Marc, Jäger, Natalie, Chavez, Lukas, Hutter, Barbara, Bieg, Matthias, Paramasivam, Nagarajan, Heinold, Michael, Gu, Zuguang, Ishaque, Naveed, Jäger-Schmidt, Christina, Imbusch, Charles D., Jugold, Alke, Hübschmann, Daniel, Risch, Thomas, Amstislavskiy, Vyacheslav, Gonzalez, Francisco German Rodriguez, Weber, Ursula D., Wolf, Stephan, Robinson, Giles W., Zhou, Xin, Wu, Gang, Finkelstein, David, Liu, Yanling, Cavalli, Florence M.G., Luu, Betty, Ramaswamy, Vijay, Wu, Xiaochong, Koster, Jan, Ryzhova, Marina, Cho, Yoon Jae, Pomeroy, Scott L., Herold-Mende, Christel, Schuhmann, Martin, Ebinger, Martin, Liau, Linda M., Mora, Jaume, McLendon, Roger E., Jabado, Nada, Kumabe, Toshihiro, Chuah, Eric, Ma, Yussanne, Moore, Richard A., Mungall, Andrew J., Mungall, Karen L., Thiessen, Nina, Tse, Kane, Wong, Tina, Jones, Steven J.M., Witt, Olaf, Milde, Till, Von Deimling, Andreas, Capper, David, Korshunov, Andrey, Yaspo, Marie Laure, Kriwacki, Richard, Gajjar, Amar, Zhang, Jinghui, Beroukhim, Rameen, Fraenkel, Ernest, Korbel, Jan O., Brors, Benedikt, Schlesner, Matthias, Eils, Roland, Marra, Marco A., Pfister, Stefan M., Taylor, Michael D., and Lichter, Peter
Abstract: Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.
Published: 2017

39. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis.

Author: Thompson, Eric M, Thompson, Eric M, Hielscher, Thomas, Bouffet, Eric, Remke, Marc, Luu, Betty, Gururangan, Sridharan, McLendon, Roger E, Bigner, Darell D, Lipp, Eric S, Perreault, Sebastien, Cho, Yoon-Jae, Grant, Gerald, Kim, Seung-Ki, Lee, Ji Yeoun, Rao, Amulya A Nageswara, Giannini, Caterina, Li, Kay Ka Wai, Ng, Ho-Keung, Yao, Yu, Kumabe, Toshihiro, Tominaga, Teiji, Grajkowska, Wieslawa A, Perek-Polnik, Marta, Low, David CY, Seow, Wan Tew, Chang, Kenneth TE, Mora, Jaume, Pollack, Ian F, Hamilton, Ronald L, Leary, Sarah, Moore, Andrew S, Ingram, Wendy J, Hallahan, Andrew R, Jouvet, Anne, Fèvre-Montange, Michelle, Vasiljevic, Alexandre, Faure-Conter, Cecile, Shofuda, Tomoko, Kagawa, Naoki, Hashimoto, Naoya, Jabado, Nada, Weil, Alexander G, Gayden, Tenzin, Wataya, Takafumi, Shalaby, Tarek, Grotzer, Michael, Zitterbart, Karel, Sterba, Jaroslav, Kren, Leos, Hortobágyi, Tibor, Klekner, Almos, László, Bognár, Pócza, Tímea, Hauser, Peter, Schüller, Ulrich, Jung, Shin, Jang, Woo-Youl, French, Pim J, Kros, Johan M, van Veelen, Marie-Lise C, Massimi, Luca, Leonard, Jeffrey R, Rubin, Joshua B, Vibhakar, Rajeev, Chambless, Lola B, Cooper, Michael K, Thompson, Reid C, Faria, Claudia C, Carvalho, Alice, Nunes, Sofia, Pimentel, José, Fan, Xing, Muraszko, Karin M, López-Aguilar, Enrique, Lyden, David, Garzia, Livia, Shih, David JH, Kijima, Noriyuki, Schneider, Christian, Adamski, Jennifer, Northcott, Paul A, Kool, Marcel, Jones, David TW, Chan, Jennifer A, Nikolic, Ana, Garre, Maria Luisa, Van Meir, Erwin G, Osuka, Satoru, Olson, Jeffrey J, Jahangiri, Arman, Castro, Brandyn A, Gupta, Nalin, Weiss, William A, Moxon-Emre, Iska, Mabbott, Donald J, Lassaletta, Alvaro, Hawkins, Cynthia E, Tabori, Uri, Drake, James, Kulkarni, Abhaya, Thompson, Eric M, Thompson, Eric M, Hielscher, Thomas, Bouffet, Eric, Remke, Marc, Luu, Betty, Gururangan, Sridharan, McLendon, Roger E, Bigner, Darell D, Lipp, Eric S, Perreault, Sebastien, Cho, Yoon-Jae, Grant, Gerald, Kim, Seung-Ki, Lee, Ji Yeoun, Rao, Amulya A Nageswara, Giannini, Caterina, Li, Kay Ka Wai, Ng, Ho-Keung, Yao, Yu, Kumabe, Toshihiro, Tominaga, Teiji, Grajkowska, Wieslawa A, Perek-Polnik, Marta, Low, David CY, Seow, Wan Tew, Chang, Kenneth TE, Mora, Jaume, Pollack, Ian F, Hamilton, Ronald L, Leary, Sarah, Moore, Andrew S, Ingram, Wendy J, Hallahan, Andrew R, Jouvet, Anne, Fèvre-Montange, Michelle, Vasiljevic, Alexandre, Faure-Conter, Cecile, Shofuda, Tomoko, Kagawa, Naoki, Hashimoto, Naoya, Jabado, Nada, Weil, Alexander G, Gayden, Tenzin, Wataya, Takafumi, Shalaby, Tarek, Grotzer, Michael, Zitterbart, Karel, Sterba, Jaroslav, Kren, Leos, Hortobágyi, Tibor, Klekner, Almos, László, Bognár, Pócza, Tímea, Hauser, Peter, Schüller, Ulrich, Jung, Shin, Jang, Woo-Youl, French, Pim J, Kros, Johan M, van Veelen, Marie-Lise C, Massimi, Luca, Leonard, Jeffrey R, Rubin, Joshua B, Vibhakar, Rajeev, Chambless, Lola B, Cooper, Michael K, Thompson, Reid C, Faria, Claudia C, Carvalho, Alice, Nunes, Sofia, Pimentel, José, Fan, Xing, Muraszko, Karin M, López-Aguilar, Enrique, Lyden, David, Garzia, Livia, Shih, David JH, Kijima, Noriyuki, Schneider, Christian, Adamski, Jennifer, Northcott, Paul A, Kool, Marcel, Jones, David TW, Chan, Jennifer A, Nikolic, Ana, Garre, Maria Luisa, Van Meir, Erwin G, Osuka, Satoru, Olson, Jeffrey J, Jahangiri, Arman, Castro, Brandyn A, Gupta, Nalin, Weiss, William A, Moxon-Emre, Iska, Mabbott, Donald J, Lassaletta, Alvaro, Hawkins, Cynthia E, Tabori, Uri, Drake, James, and Kulkarni, Abhaya
Abstract: BackgroundPatients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner.MethodsWe retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (<1·5 cm(2) tumour remaining), or sub-total resection (≥1·5 cm(2) tumour remaining). We did multivariable analyses of overall survival and progression-free survival using the variables molecular subgroup (WNT, SHH, group 4, and group 3), age (<3 vs ≥3 years old), metastatic status (metastases vs no metastases), geographical location of therapy (North America/Australia vs rest of the world), receipt of chemotherapy (yes vs no) and receipt of craniospinal irradiation (<30 Gy or >30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival.FindingsWe included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable
Published: 2016

40. Medulloblastoma-associated DDX3 variant selectively alters the translational response to stress.

Author: Oh, Sekyung, Oh, Sekyung, Flynn, Ryan A, Floor, Stephen N, Purzner, James, Martin, Lance, Do, Brian T, Schubert, Simone, Vaka, Dedeepya, Morrissy, Sorana, Li, Yisu, Kool, Marcel, Hovestadt, Volker, Jones, David TW, Northcott, Paul A, Risch, Thomas, Warnatz, Hans-Jörg, Yaspo, Marie-Laure, Adams, Christopher M, Leib, Ryan D, Breese, Marcus, Marra, Marco A, Malkin, David, Lichter, Peter, Doudna, Jennifer A, Pfister, Stefan M, Taylor, Michael D, Chang, Howard Y, Cho, Yoon-Jae, Oh, Sekyung, Oh, Sekyung, Flynn, Ryan A, Floor, Stephen N, Purzner, James, Martin, Lance, Do, Brian T, Schubert, Simone, Vaka, Dedeepya, Morrissy, Sorana, Li, Yisu, Kool, Marcel, Hovestadt, Volker, Jones, David TW, Northcott, Paul A, Risch, Thomas, Warnatz, Hans-Jörg, Yaspo, Marie-Laure, Adams, Christopher M, Leib, Ryan D, Breese, Marcus, Marra, Marco A, Malkin, David, Lichter, Peter, Doudna, Jennifer A, Pfister, Stefan M, Taylor, Michael D, Chang, Howard Y, and Cho, Yoon-Jae
Abstract: DDX3X encodes a DEAD-box family RNA helicase (DDX3) commonly mutated in medulloblastoma, a highly aggressive cerebellar tumor affecting both children and adults. Despite being implicated in several facets of RNA metabolism, the nature and scope of DDX3's interactions with RNA remain unclear. Here, we show DDX3 collaborates extensively with the translation initiation machinery through direct binding to 5'UTRs of nearly all coding RNAs, specific sites on the 18S rRNA, and multiple components of the translation initiation complex. Impairment of translation initiation is also evident in primary medulloblastomas harboring mutations in DDX3X, further highlighting DDX3's role in this process. Arsenite-induced stress shifts DDX3 binding from the 5'UTR into the coding region of mRNAs concomitant with a general reduction of translation, and both the shift of DDX3 on mRNA and decreased translation are blunted by expression of a catalytically-impaired, medulloblastoma-associated DDX3R534H variant. Furthermore, despite the global repression of translation induced by arsenite, translation is preserved on select genes involved in chromatin organization in DDX3R534H-expressing cells. Thus, DDX3 interacts extensively with RNA and ribosomal machinery to help remodel the translation landscape in response to stress, while cancer-related DDX3 variants adapt this response to selectively preserve translation.
Published: 2016

41. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

Author: Sturm, Dominik, Orr, Brent A., Toprak, Umut H., Hovestadt, Volker, Jones, David T W, Capper, David, Sill, Martin, Buchhalter, Ivo, Northcott, Paul A., Leis, Irina, Ryzhova, Marina, Koelsche, Christian, Pfaff, Elke, Allen, Sariah J., Balasubramanian, Gnanaprakash, Worst, Barbara C., Pajtler, Kristian W., Brabetz, Sebastian, Johann, Pascal D., Sahm, Felix, Reimand, Jüri, Mackay, Alan, Carvalho, Diana M., Remke, Marc, Phillips, Joanna J., Perry, Arie, Cowdrey, Cynthia, Drissi, Rachid, Fouladi, Maryam, Giangaspero, Felice, Łastowska, Maria, Grajkowska, Wiesława, Scheurlen, Wolfram, Pietsch, Torsten, Hagel, Christian, Gojo, Johannes, Lötsch, Daniela, Berger, Walter, Slavc, Irene, Haberler, Christine, Jouvet, Anne, Holm, Stefan, Hofer, Silvia, Prinz, Marco, Keohane, Catherine, Fried, Iris, Mawrin, Christian, Scheie, David, Mobley, Bret C., Schniederjan, Matthew J., Santi, Mariarita, Buccoliero, Anna M., Dahiya, Sonika, Kramm, Christof M., Von Bueren, André O., Von Hoff, Katja, Rutkowski, Stefan, Herold-Mende, Christel, Frühwald, Michael C., Milde, Till, Hasselblatt, Martin, Wesseling, Pieter, Rößler, Jochen, Schüller, Ulrich, Ebinger, Martin, Schittenhelm, Jens, Frank, Stephan, Grobholz, Rainer, Vajtai, Istvan, Hans, Volkmar, Schneppenheim, Reinhard, Zitterbart, Karel, Collins, V. Peter, Aronica, Eleonora, Varlet, Pascale, Puget, Stephanie, Dufour, Christelle, Grill, Jacques, Figarella-Branger, Dominique, Wolter, Marietta, Schuhmann, Martin U., Shalaby, Tarek, Grotzer, Michael, Van Meter, Timothy, Monoranu, Camelia Maria, Felsberg, Jörg, Reifenberger, Guido, Snuderl, Matija, Forrester, Lynn Ann, Koster, Jan, Versteeg, Rogier, Volckmann, Richard, Van Sluis, Peter, Wolf, Stephan, Mikkelsen, Tom, Gajjar, Amar, Aldape, Kenneth, Moore, Andrew S., Taylor, Michael D., Jones, Chris, Jabado, Nada, Karajannis, Matthias A., Eils, Roland, Schlesner, Matthias, Lichter, Peter, Von Deimling, Andreas, Pfister, Stefan M., Ellison, David W., Korshunov, Andrey, Kool, Marcel, Sturm, Dominik, Orr, Brent A., Toprak, Umut H., Hovestadt, Volker, Jones, David T W, Capper, David, Sill, Martin, Buchhalter, Ivo, Northcott, Paul A., Leis, Irina, Ryzhova, Marina, Koelsche, Christian, Pfaff, Elke, Allen, Sariah J., Balasubramanian, Gnanaprakash, Worst, Barbara C., Pajtler, Kristian W., Brabetz, Sebastian, Johann, Pascal D., Sahm, Felix, Reimand, Jüri, Mackay, Alan, Carvalho, Diana M., Remke, Marc, Phillips, Joanna J., Perry, Arie, Cowdrey, Cynthia, Drissi, Rachid, Fouladi, Maryam, Giangaspero, Felice, Łastowska, Maria, Grajkowska, Wiesława, Scheurlen, Wolfram, Pietsch, Torsten, Hagel, Christian, Gojo, Johannes, Lötsch, Daniela, Berger, Walter, Slavc, Irene, Haberler, Christine, Jouvet, Anne, Holm, Stefan, Hofer, Silvia, Prinz, Marco, Keohane, Catherine, Fried, Iris, Mawrin, Christian, Scheie, David, Mobley, Bret C., Schniederjan, Matthew J., Santi, Mariarita, Buccoliero, Anna M., Dahiya, Sonika, Kramm, Christof M., Von Bueren, André O., Von Hoff, Katja, Rutkowski, Stefan, Herold-Mende, Christel, Frühwald, Michael C., Milde, Till, Hasselblatt, Martin, Wesseling, Pieter, Rößler, Jochen, Schüller, Ulrich, Ebinger, Martin, Schittenhelm, Jens, Frank, Stephan, Grobholz, Rainer, Vajtai, Istvan, Hans, Volkmar, Schneppenheim, Reinhard, Zitterbart, Karel, Collins, V. Peter, Aronica, Eleonora, Varlet, Pascale, Puget, Stephanie, Dufour, Christelle, Grill, Jacques, Figarella-Branger, Dominique, Wolter, Marietta, Schuhmann, Martin U., Shalaby, Tarek, Grotzer, Michael, Van Meter, Timothy, Monoranu, Camelia Maria, Felsberg, Jörg, Reifenberger, Guido, Snuderl, Matija, Forrester, Lynn Ann, Koster, Jan, Versteeg, Rogier, Volckmann, Richard, Van Sluis, Peter, Wolf, Stephan, Mikkelsen, Tom, Gajjar, Amar, Aldape, Kenneth, Moore, Andrew S., Taylor, Michael D., Jones, Chris, Jabado, Nada, Karajannis, Matthias A., Eils, Roland, Schlesner, Matthias, Lichter, Peter, Von Deimling, Andreas, Pfister, Stefan M., Ellison, David W., Korshunov, Andrey, and Kool, Marcel
Published: 2016

42. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

Author: Sturm, Dominik, Orr, Brent A., Toprak, Umut H., Hovestadt, Volker, Jones, David T W, Capper, David, Sill, Martin, Buchhalter, Ivo, Northcott, Paul A., Leis, Irina, Ryzhova, Marina, Koelsche, Christian, Pfaff, Elke, Allen, Sariah J., Balasubramanian, Gnanaprakash, Worst, Barbara C., Pajtler, Kristian W., Brabetz, Sebastian, Johann, Pascal D., Sahm, Felix, Reimand, Jüri, Mackay, Alan, Carvalho, Diana M., Remke, Marc, Phillips, Joanna J., Perry, Arie, Cowdrey, Cynthia, Drissi, Rachid, Fouladi, Maryam, Giangaspero, Felice, Łastowska, Maria, Grajkowska, Wiesława, Scheurlen, Wolfram, Pietsch, Torsten, Hagel, Christian, Gojo, Johannes, Lötsch, Daniela, Berger, Walter, Slavc, Irene, Haberler, Christine, Jouvet, Anne, Holm, Stefan, Hofer, Silvia, Prinz, Marco, Keohane, Catherine, Fried, Iris, Mawrin, Christian, Scheie, David, Mobley, Bret C., Schniederjan, Matthew J., Santi, Mariarita, Buccoliero, Anna M., Dahiya, Sonika, Kramm, Christof M., Von Bueren, André O., Von Hoff, Katja, Rutkowski, Stefan, Herold-Mende, Christel, Frühwald, Michael C., Milde, Till, Hasselblatt, Martin, Wesseling, Pieter, Rößler, Jochen, Schüller, Ulrich, Ebinger, Martin, Schittenhelm, Jens, Frank, Stephan, Grobholz, Rainer, Vajtai, Istvan, Hans, Volkmar, Schneppenheim, Reinhard, Zitterbart, Karel, Collins, V. Peter, Aronica, Eleonora, Varlet, Pascale, Puget, Stephanie, Dufour, Christelle, Grill, Jacques, Figarella-Branger, Dominique, Wolter, Marietta, Schuhmann, Martin U., Shalaby, Tarek, Grotzer, Michael, Van Meter, Timothy, Monoranu, Camelia Maria, Felsberg, Jörg, Reifenberger, Guido, Snuderl, Matija, Forrester, Lynn Ann, Koster, Jan, Versteeg, Rogier, Volckmann, Richard, Van Sluis, Peter, Wolf, Stephan, Mikkelsen, Tom, Gajjar, Amar, Aldape, Kenneth, Moore, Andrew S., Taylor, Michael D., Jones, Chris, Jabado, Nada, Karajannis, Matthias A., Eils, Roland, Schlesner, Matthias, Lichter, Peter, Von Deimling, Andreas, Pfister, Stefan M., Ellison, David W., Korshunov, Andrey, Kool, Marcel, Sturm, Dominik, Orr, Brent A., Toprak, Umut H., Hovestadt, Volker, Jones, David T W, Capper, David, Sill, Martin, Buchhalter, Ivo, Northcott, Paul A., Leis, Irina, Ryzhova, Marina, Koelsche, Christian, Pfaff, Elke, Allen, Sariah J., Balasubramanian, Gnanaprakash, Worst, Barbara C., Pajtler, Kristian W., Brabetz, Sebastian, Johann, Pascal D., Sahm, Felix, Reimand, Jüri, Mackay, Alan, Carvalho, Diana M., Remke, Marc, Phillips, Joanna J., Perry, Arie, Cowdrey, Cynthia, Drissi, Rachid, Fouladi, Maryam, Giangaspero, Felice, Łastowska, Maria, Grajkowska, Wiesława, Scheurlen, Wolfram, Pietsch, Torsten, Hagel, Christian, Gojo, Johannes, Lötsch, Daniela, Berger, Walter, Slavc, Irene, Haberler, Christine, Jouvet, Anne, Holm, Stefan, Hofer, Silvia, Prinz, Marco, Keohane, Catherine, Fried, Iris, Mawrin, Christian, Scheie, David, Mobley, Bret C., Schniederjan, Matthew J., Santi, Mariarita, Buccoliero, Anna M., Dahiya, Sonika, Kramm, Christof M., Von Bueren, André O., Von Hoff, Katja, Rutkowski, Stefan, Herold-Mende, Christel, Frühwald, Michael C., Milde, Till, Hasselblatt, Martin, Wesseling, Pieter, Rößler, Jochen, Schüller, Ulrich, Ebinger, Martin, Schittenhelm, Jens, Frank, Stephan, Grobholz, Rainer, Vajtai, Istvan, Hans, Volkmar, Schneppenheim, Reinhard, Zitterbart, Karel, Collins, V. Peter, Aronica, Eleonora, Varlet, Pascale, Puget, Stephanie, Dufour, Christelle, Grill, Jacques, Figarella-Branger, Dominique, Wolter, Marietta, Schuhmann, Martin U., Shalaby, Tarek, Grotzer, Michael, Van Meter, Timothy, Monoranu, Camelia Maria, Felsberg, Jörg, Reifenberger, Guido, Snuderl, Matija, Forrester, Lynn Ann, Koster, Jan, Versteeg, Rogier, Volckmann, Richard, Van Sluis, Peter, Wolf, Stephan, Mikkelsen, Tom, Gajjar, Amar, Aldape, Kenneth, Moore, Andrew S., Taylor, Michael D., Jones, Chris, Jabado, Nada, Karajannis, Matthias A., Eils, Roland, Schlesner, Matthias, Lichter, Peter, Von Deimling, Andreas, Pfister, Stefan M., Ellison, David W., Korshunov, Andrey, and Kool, Marcel
Published: 2016

43. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis.

Author: Thompson, Eric M, Thompson, Eric M, Hielscher, Thomas, Bouffet, Eric, Remke, Marc, Luu, Betty, Gururangan, Sridharan, McLendon, Roger E, Bigner, Darell D, Lipp, Eric S, Perreault, Sebastien, Cho, Yoon-Jae, Grant, Gerald, Kim, Seung-Ki, Lee, Ji Yeoun, Rao, Amulya A Nageswara, Giannini, Caterina, Li, Kay Ka Wai, Ng, Ho-Keung, Yao, Yu, Kumabe, Toshihiro, Tominaga, Teiji, Grajkowska, Wieslawa A, Perek-Polnik, Marta, Low, David CY, Seow, Wan Tew, Chang, Kenneth TE, Mora, Jaume, Pollack, Ian F, Hamilton, Ronald L, Leary, Sarah, Moore, Andrew S, Ingram, Wendy J, Hallahan, Andrew R, Jouvet, Anne, Fèvre-Montange, Michelle, Vasiljevic, Alexandre, Faure-Conter, Cecile, Shofuda, Tomoko, Kagawa, Naoki, Hashimoto, Naoya, Jabado, Nada, Weil, Alexander G, Gayden, Tenzin, Wataya, Takafumi, Shalaby, Tarek, Grotzer, Michael, Zitterbart, Karel, Sterba, Jaroslav, Kren, Leos, Hortobágyi, Tibor, Klekner, Almos, László, Bognár, Pócza, Tímea, Hauser, Peter, Schüller, Ulrich, Jung, Shin, Jang, Woo-Youl, French, Pim J, Kros, Johan M, van Veelen, Marie-Lise C, Massimi, Luca, Leonard, Jeffrey R, Rubin, Joshua B, Vibhakar, Rajeev, Chambless, Lola B, Cooper, Michael K, Thompson, Reid C, Faria, Claudia C, Carvalho, Alice, Nunes, Sofia, Pimentel, José, Fan, Xing, Muraszko, Karin M, López-Aguilar, Enrique, Lyden, David, Garzia, Livia, Shih, David JH, Kijima, Noriyuki, Schneider, Christian, Adamski, Jennifer, Northcott, Paul A, Kool, Marcel, Jones, David TW, Chan, Jennifer A, Nikolic, Ana, Garre, Maria Luisa, Van Meir, Erwin G, Osuka, Satoru, Olson, Jeffrey J, Jahangiri, Arman, Castro, Brandyn A, Gupta, Nalin, Weiss, William A, Moxon-Emre, Iska, Mabbott, Donald J, Lassaletta, Alvaro, Hawkins, Cynthia E, Tabori, Uri, Drake, James, Kulkarni, Abhaya, Thompson, Eric M, Thompson, Eric M, Hielscher, Thomas, Bouffet, Eric, Remke, Marc, Luu, Betty, Gururangan, Sridharan, McLendon, Roger E, Bigner, Darell D, Lipp, Eric S, Perreault, Sebastien, Cho, Yoon-Jae, Grant, Gerald, Kim, Seung-Ki, Lee, Ji Yeoun, Rao, Amulya A Nageswara, Giannini, Caterina, Li, Kay Ka Wai, Ng, Ho-Keung, Yao, Yu, Kumabe, Toshihiro, Tominaga, Teiji, Grajkowska, Wieslawa A, Perek-Polnik, Marta, Low, David CY, Seow, Wan Tew, Chang, Kenneth TE, Mora, Jaume, Pollack, Ian F, Hamilton, Ronald L, Leary, Sarah, Moore, Andrew S, Ingram, Wendy J, Hallahan, Andrew R, Jouvet, Anne, Fèvre-Montange, Michelle, Vasiljevic, Alexandre, Faure-Conter, Cecile, Shofuda, Tomoko, Kagawa, Naoki, Hashimoto, Naoya, Jabado, Nada, Weil, Alexander G, Gayden, Tenzin, Wataya, Takafumi, Shalaby, Tarek, Grotzer, Michael, Zitterbart, Karel, Sterba, Jaroslav, Kren, Leos, Hortobágyi, Tibor, Klekner, Almos, László, Bognár, Pócza, Tímea, Hauser, Peter, Schüller, Ulrich, Jung, Shin, Jang, Woo-Youl, French, Pim J, Kros, Johan M, van Veelen, Marie-Lise C, Massimi, Luca, Leonard, Jeffrey R, Rubin, Joshua B, Vibhakar, Rajeev, Chambless, Lola B, Cooper, Michael K, Thompson, Reid C, Faria, Claudia C, Carvalho, Alice, Nunes, Sofia, Pimentel, José, Fan, Xing, Muraszko, Karin M, López-Aguilar, Enrique, Lyden, David, Garzia, Livia, Shih, David JH, Kijima, Noriyuki, Schneider, Christian, Adamski, Jennifer, Northcott, Paul A, Kool, Marcel, Jones, David TW, Chan, Jennifer A, Nikolic, Ana, Garre, Maria Luisa, Van Meir, Erwin G, Osuka, Satoru, Olson, Jeffrey J, Jahangiri, Arman, Castro, Brandyn A, Gupta, Nalin, Weiss, William A, Moxon-Emre, Iska, Mabbott, Donald J, Lassaletta, Alvaro, Hawkins, Cynthia E, Tabori, Uri, Drake, James, and Kulkarni, Abhaya
Abstract: BackgroundPatients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner.MethodsWe retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (<1·5 cm(2) tumour remaining), or sub-total resection (≥1·5 cm(2) tumour remaining). We did multivariable analyses of overall survival and progression-free survival using the variables molecular subgroup (WNT, SHH, group 4, and group 3), age (<3 vs ≥3 years old), metastatic status (metastases vs no metastases), geographical location of therapy (North America/Australia vs rest of the world), receipt of chemotherapy (yes vs no) and receipt of craniospinal irradiation (<30 Gy or >30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival.FindingsWe included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable
Published: 2016

44. Medulloblastoma-associated DDX3 variant selectively alters the translational response to stress.

Author: Oh, Sekyung, Oh, Sekyung, Flynn, Ryan A, Floor, Stephen N, Purzner, James, Martin, Lance, Do, Brian T, Schubert, Simone, Vaka, Dedeepya, Morrissy, Sorana, Li, Yisu, Kool, Marcel, Hovestadt, Volker, Jones, David TW, Northcott, Paul A, Risch, Thomas, Warnatz, Hans-Jörg, Yaspo, Marie-Laure, Adams, Christopher M, Leib, Ryan D, Breese, Marcus, Marra, Marco A, Malkin, David, Lichter, Peter, Doudna, Jennifer A, Pfister, Stefan M, Taylor, Michael D, Chang, Howard Y, Cho, Yoon-Jae, Oh, Sekyung, Oh, Sekyung, Flynn, Ryan A, Floor, Stephen N, Purzner, James, Martin, Lance, Do, Brian T, Schubert, Simone, Vaka, Dedeepya, Morrissy, Sorana, Li, Yisu, Kool, Marcel, Hovestadt, Volker, Jones, David TW, Northcott, Paul A, Risch, Thomas, Warnatz, Hans-Jörg, Yaspo, Marie-Laure, Adams, Christopher M, Leib, Ryan D, Breese, Marcus, Marra, Marco A, Malkin, David, Lichter, Peter, Doudna, Jennifer A, Pfister, Stefan M, Taylor, Michael D, Chang, Howard Y, and Cho, Yoon-Jae
Abstract: DDX3X encodes a DEAD-box family RNA helicase (DDX3) commonly mutated in medulloblastoma, a highly aggressive cerebellar tumor affecting both children and adults. Despite being implicated in several facets of RNA metabolism, the nature and scope of DDX3's interactions with RNA remain unclear. Here, we show DDX3 collaborates extensively with the translation initiation machinery through direct binding to 5'UTRs of nearly all coding RNAs, specific sites on the 18S rRNA, and multiple components of the translation initiation complex. Impairment of translation initiation is also evident in primary medulloblastomas harboring mutations in DDX3X, further highlighting DDX3's role in this process. Arsenite-induced stress shifts DDX3 binding from the 5'UTR into the coding region of mRNAs concomitant with a general reduction of translation, and both the shift of DDX3 on mRNA and decreased translation are blunted by expression of a catalytically-impaired, medulloblastoma-associated DDX3R534H variant. Furthermore, despite the global repression of translation induced by arsenite, translation is preserved on select genes involved in chromatin organization in DDX3R534H-expressing cells. Thus, DDX3 interacts extensively with RNA and ribosomal machinery to help remodel the translation landscape in response to stress, while cancer-related DDX3 variants adapt this response to selectively preserve translation.
Published: 2016

45. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

Author: Sturm, Dominik, Orr, Brent A., Toprak, Umut H., Hovestadt, Volker, Jones, David T W, Capper, David, Sill, Martin, Buchhalter, Ivo, Northcott, Paul A., Leis, Irina, Ryzhova, Marina, Koelsche, Christian, Pfaff, Elke, Allen, Sariah J., Balasubramanian, Gnanaprakash, Worst, Barbara C., Pajtler, Kristian W., Brabetz, Sebastian, Johann, Pascal D., Sahm, Felix, Reimand, Jüri, Mackay, Alan, Carvalho, Diana M., Remke, Marc, Phillips, Joanna J., Perry, Arie, Cowdrey, Cynthia, Drissi, Rachid, Fouladi, Maryam, Giangaspero, Felice, Łastowska, Maria, Grajkowska, Wiesława, Scheurlen, Wolfram, Pietsch, Torsten, Hagel, Christian, Gojo, Johannes, Lötsch, Daniela, Berger, Walter, Slavc, Irene, Haberler, Christine, Jouvet, Anne, Holm, Stefan, Hofer, Silvia, Prinz, Marco, Keohane, Catherine, Fried, Iris, Mawrin, Christian, Scheie, David, Mobley, Bret C., Schniederjan, Matthew J., Santi, Mariarita, Buccoliero, Anna M., Dahiya, Sonika, Kramm, Christof M., Von Bueren, André O., Von Hoff, Katja, Rutkowski, Stefan, Herold-Mende, Christel, Frühwald, Michael C., Milde, Till, Hasselblatt, Martin, Wesseling, Pieter, Rößler, Jochen, Schüller, Ulrich, Ebinger, Martin, Schittenhelm, Jens, Frank, Stephan, Grobholz, Rainer, Vajtai, Istvan, Hans, Volkmar, Schneppenheim, Reinhard, Zitterbart, Karel, Collins, V. Peter, Aronica, Eleonora, Varlet, Pascale, Puget, Stephanie, Dufour, Christelle, Grill, Jacques, Figarella-Branger, Dominique, Wolter, Marietta, Schuhmann, Martin U., Shalaby, Tarek, Grotzer, Michael, Van Meter, Timothy, Monoranu, Camelia Maria, Felsberg, Jörg, Reifenberger, Guido, Snuderl, Matija, Forrester, Lynn Ann, Koster, Jan, Versteeg, Rogier, Volckmann, Richard, Van Sluis, Peter, Wolf, Stephan, Mikkelsen, Tom, Gajjar, Amar, Aldape, Kenneth, Moore, Andrew S., Taylor, Michael D., Jones, Chris, Jabado, Nada, Karajannis, Matthias A., Eils, Roland, Schlesner, Matthias, Lichter, Peter, Von Deimling, Andreas, Pfister, Stefan M., Ellison, David W., Korshunov, Andrey, Kool, Marcel, Sturm, Dominik, Orr, Brent A., Toprak, Umut H., Hovestadt, Volker, Jones, David T W, Capper, David, Sill, Martin, Buchhalter, Ivo, Northcott, Paul A., Leis, Irina, Ryzhova, Marina, Koelsche, Christian, Pfaff, Elke, Allen, Sariah J., Balasubramanian, Gnanaprakash, Worst, Barbara C., Pajtler, Kristian W., Brabetz, Sebastian, Johann, Pascal D., Sahm, Felix, Reimand, Jüri, Mackay, Alan, Carvalho, Diana M., Remke, Marc, Phillips, Joanna J., Perry, Arie, Cowdrey, Cynthia, Drissi, Rachid, Fouladi, Maryam, Giangaspero, Felice, Łastowska, Maria, Grajkowska, Wiesława, Scheurlen, Wolfram, Pietsch, Torsten, Hagel, Christian, Gojo, Johannes, Lötsch, Daniela, Berger, Walter, Slavc, Irene, Haberler, Christine, Jouvet, Anne, Holm, Stefan, Hofer, Silvia, Prinz, Marco, Keohane, Catherine, Fried, Iris, Mawrin, Christian, Scheie, David, Mobley, Bret C., Schniederjan, Matthew J., Santi, Mariarita, Buccoliero, Anna M., Dahiya, Sonika, Kramm, Christof M., Von Bueren, André O., Von Hoff, Katja, Rutkowski, Stefan, Herold-Mende, Christel, Frühwald, Michael C., Milde, Till, Hasselblatt, Martin, Wesseling, Pieter, Rößler, Jochen, Schüller, Ulrich, Ebinger, Martin, Schittenhelm, Jens, Frank, Stephan, Grobholz, Rainer, Vajtai, Istvan, Hans, Volkmar, Schneppenheim, Reinhard, Zitterbart, Karel, Collins, V. Peter, Aronica, Eleonora, Varlet, Pascale, Puget, Stephanie, Dufour, Christelle, Grill, Jacques, Figarella-Branger, Dominique, Wolter, Marietta, Schuhmann, Martin U., Shalaby, Tarek, Grotzer, Michael, Van Meter, Timothy, Monoranu, Camelia Maria, Felsberg, Jörg, Reifenberger, Guido, Snuderl, Matija, Forrester, Lynn Ann, Koster, Jan, Versteeg, Rogier, Volckmann, Richard, Van Sluis, Peter, Wolf, Stephan, Mikkelsen, Tom, Gajjar, Amar, Aldape, Kenneth, Moore, Andrew S., Taylor, Michael D., Jones, Chris, Jabado, Nada, Karajannis, Matthias A., Eils, Roland, Schlesner, Matthias, Lichter, Peter, Von Deimling, Andreas, Pfister, Stefan M., Ellison, David W., Korshunov, Andrey, and Kool, Marcel
Published: 2016

46. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.

Author: Sturm, Dominik, Sturm, Dominik, Orr, Brent A, Toprak, Umut H, Hovestadt, Volker, Jones, David TW, Capper, David, Sill, Martin, Buchhalter, Ivo, Northcott, Paul A, Leis, Irina, Ryzhova, Marina, Koelsche, Christian, Pfaff, Elke, Allen, Sariah J, Balasubramanian, Gnanaprakash, Worst, Barbara C, Pajtler, Kristian W, Brabetz, Sebastian, Johann, Pascal D, Sahm, Felix, Reimand, Jüri, Mackay, Alan, Carvalho, Diana M, Remke, Marc, Phillips, Joanna J, Perry, Arie, Cowdrey, Cynthia, Drissi, Rachid, Fouladi, Maryam, Giangaspero, Felice, Łastowska, Maria, Grajkowska, Wiesława, Scheurlen, Wolfram, Pietsch, Torsten, Hagel, Christian, Gojo, Johannes, Lötsch, Daniela, Berger, Walter, Slavc, Irene, Haberler, Christine, Jouvet, Anne, Holm, Stefan, Hofer, Silvia, Prinz, Marco, Keohane, Catherine, Fried, Iris, Mawrin, Christian, Scheie, David, Mobley, Bret C, Schniederjan, Matthew J, Santi, Mariarita, Buccoliero, Anna M, Dahiya, Sonika, Kramm, Christof M, von Bueren, André O, von Hoff, Katja, Rutkowski, Stefan, Herold-Mende, Christel, Frühwald, Michael C, Milde, Till, Hasselblatt, Martin, Wesseling, Pieter, Rößler, Jochen, Schüller, Ulrich, Ebinger, Martin, Schittenhelm, Jens, Frank, Stephan, Grobholz, Rainer, Vajtai, Istvan, Hans, Volkmar, Schneppenheim, Reinhard, Zitterbart, Karel, Collins, V Peter, Aronica, Eleonora, Varlet, Pascale, Puget, Stephanie, Dufour, Christelle, Grill, Jacques, Figarella-Branger, Dominique, Wolter, Marietta, Schuhmann, Martin U, Shalaby, Tarek, Grotzer, Michael, van Meter, Timothy, Monoranu, Camelia-Maria, Felsberg, Jörg, Reifenberger, Guido, Snuderl, Matija, Forrester, Lynn Ann, Koster, Jan, Versteeg, Rogier, Volckmann, Richard, van Sluis, Peter, Wolf, Stephan, Mikkelsen, Tom, Gajjar, Amar, Aldape, Kenneth, Moore, Andrew S, Taylor, Michael D, Jones, Chris, Sturm, Dominik, Sturm, Dominik, Orr, Brent A, Toprak, Umut H, Hovestadt, Volker, Jones, David TW, Capper, David, Sill, Martin, Buchhalter, Ivo, Northcott, Paul A, Leis, Irina, Ryzhova, Marina, Koelsche, Christian, Pfaff, Elke, Allen, Sariah J, Balasubramanian, Gnanaprakash, Worst, Barbara C, Pajtler, Kristian W, Brabetz, Sebastian, Johann, Pascal D, Sahm, Felix, Reimand, Jüri, Mackay, Alan, Carvalho, Diana M, Remke, Marc, Phillips, Joanna J, Perry, Arie, Cowdrey, Cynthia, Drissi, Rachid, Fouladi, Maryam, Giangaspero, Felice, Łastowska, Maria, Grajkowska, Wiesława, Scheurlen, Wolfram, Pietsch, Torsten, Hagel, Christian, Gojo, Johannes, Lötsch, Daniela, Berger, Walter, Slavc, Irene, Haberler, Christine, Jouvet, Anne, Holm, Stefan, Hofer, Silvia, Prinz, Marco, Keohane, Catherine, Fried, Iris, Mawrin, Christian, Scheie, David, Mobley, Bret C, Schniederjan, Matthew J, Santi, Mariarita, Buccoliero, Anna M, Dahiya, Sonika, Kramm, Christof M, von Bueren, André O, von Hoff, Katja, Rutkowski, Stefan, Herold-Mende, Christel, Frühwald, Michael C, Milde, Till, Hasselblatt, Martin, Wesseling, Pieter, Rößler, Jochen, Schüller, Ulrich, Ebinger, Martin, Schittenhelm, Jens, Frank, Stephan, Grobholz, Rainer, Vajtai, Istvan, Hans, Volkmar, Schneppenheim, Reinhard, Zitterbart, Karel, Collins, V Peter, Aronica, Eleonora, Varlet, Pascale, Puget, Stephanie, Dufour, Christelle, Grill, Jacques, Figarella-Branger, Dominique, Wolter, Marietta, Schuhmann, Martin U, Shalaby, Tarek, Grotzer, Michael, van Meter, Timothy, Monoranu, Camelia-Maria, Felsberg, Jörg, Reifenberger, Guido, Snuderl, Matija, Forrester, Lynn Ann, Koster, Jan, Versteeg, Rogier, Volckmann, Richard, van Sluis, Peter, Wolf, Stephan, Mikkelsen, Tom, Gajjar, Amar, Aldape, Kenneth, Moore, Andrew S, Taylor, Michael D, and Jones, Chris
Abstract: Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.
Published: 2016

47. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

Author: Pathologie patiënten zorg, Pathologie, Cancer, Sturm, Dominik, Orr, Brent A., Toprak, Umut H., Hovestadt, Volker, Jones, David T W, Capper, David, Sill, Martin, Buchhalter, Ivo, Northcott, Paul A., Leis, Irina, Ryzhova, Marina, Koelsche, Christian, Pfaff, Elke, Allen, Sariah J., Balasubramanian, Gnanaprakash, Worst, Barbara C., Pajtler, Kristian W., Brabetz, Sebastian, Johann, Pascal D., Sahm, Felix, Reimand, Jüri, Mackay, Alan, Carvalho, Diana M., Remke, Marc, Phillips, Joanna J., Perry, Arie, Cowdrey, Cynthia, Drissi, Rachid, Fouladi, Maryam, Giangaspero, Felice, Łastowska, Maria, Grajkowska, Wiesława, Scheurlen, Wolfram, Pietsch, Torsten, Hagel, Christian, Gojo, Johannes, Lötsch, Daniela, Berger, Walter, Slavc, Irene, Haberler, Christine, Jouvet, Anne, Holm, Stefan, Hofer, Silvia, Prinz, Marco, Keohane, Catherine, Fried, Iris, Mawrin, Christian, Scheie, David, Mobley, Bret C., Schniederjan, Matthew J., Santi, Mariarita, Buccoliero, Anna M., Dahiya, Sonika, Kramm, Christof M., Von Bueren, André O., Von Hoff, Katja, Rutkowski, Stefan, Herold-Mende, Christel, Frühwald, Michael C., Milde, Till, Hasselblatt, Martin, Wesseling, Pieter, Rößler, Jochen, Schüller, Ulrich, Ebinger, Martin, Schittenhelm, Jens, Frank, Stephan, Grobholz, Rainer, Vajtai, Istvan, Hans, Volkmar, Schneppenheim, Reinhard, Zitterbart, Karel, Collins, V. Peter, Aronica, Eleonora, Varlet, Pascale, Puget, Stephanie, Dufour, Christelle, Grill, Jacques, Figarella-Branger, Dominique, Wolter, Marietta, Schuhmann, Martin U., Shalaby, Tarek, Grotzer, Michael, Van Meter, Timothy, Monoranu, Camelia Maria, Felsberg, Jörg, Reifenberger, Guido, Snuderl, Matija, Forrester, Lynn Ann, Koster, Jan, Versteeg, Rogier, Volckmann, Richard, Van Sluis, Peter, Wolf, Stephan, Mikkelsen, Tom, Gajjar, Amar, Aldape, Kenneth, Moore, Andrew S., Taylor, Michael D., Jones, Chris, Jabado, Nada, Karajannis, Matthias A., Eils, Roland, Schlesner, Matthias, Lichter, Peter, Von Deimling, Andreas, Pfister, Stefan M., Ellison, David W., Korshunov, Andrey, Kool, Marcel, Pathologie patiënten zorg, Pathologie, Cancer, Sturm, Dominik, Orr, Brent A., Toprak, Umut H., Hovestadt, Volker, Jones, David T W, Capper, David, Sill, Martin, Buchhalter, Ivo, Northcott, Paul A., Leis, Irina, Ryzhova, Marina, Koelsche, Christian, Pfaff, Elke, Allen, Sariah J., Balasubramanian, Gnanaprakash, Worst, Barbara C., Pajtler, Kristian W., Brabetz, Sebastian, Johann, Pascal D., Sahm, Felix, Reimand, Jüri, Mackay, Alan, Carvalho, Diana M., Remke, Marc, Phillips, Joanna J., Perry, Arie, Cowdrey, Cynthia, Drissi, Rachid, Fouladi, Maryam, Giangaspero, Felice, Łastowska, Maria, Grajkowska, Wiesława, Scheurlen, Wolfram, Pietsch, Torsten, Hagel, Christian, Gojo, Johannes, Lötsch, Daniela, Berger, Walter, Slavc, Irene, Haberler, Christine, Jouvet, Anne, Holm, Stefan, Hofer, Silvia, Prinz, Marco, Keohane, Catherine, Fried, Iris, Mawrin, Christian, Scheie, David, Mobley, Bret C., Schniederjan, Matthew J., Santi, Mariarita, Buccoliero, Anna M., Dahiya, Sonika, Kramm, Christof M., Von Bueren, André O., Von Hoff, Katja, Rutkowski, Stefan, Herold-Mende, Christel, Frühwald, Michael C., Milde, Till, Hasselblatt, Martin, Wesseling, Pieter, Rößler, Jochen, Schüller, Ulrich, Ebinger, Martin, Schittenhelm, Jens, Frank, Stephan, Grobholz, Rainer, Vajtai, Istvan, Hans, Volkmar, Schneppenheim, Reinhard, Zitterbart, Karel, Collins, V. Peter, Aronica, Eleonora, Varlet, Pascale, Puget, Stephanie, Dufour, Christelle, Grill, Jacques, Figarella-Branger, Dominique, Wolter, Marietta, Schuhmann, Martin U., Shalaby, Tarek, Grotzer, Michael, Van Meter, Timothy, Monoranu, Camelia Maria, Felsberg, Jörg, Reifenberger, Guido, Snuderl, Matija, Forrester, Lynn Ann, Koster, Jan, Versteeg, Rogier, Volckmann, Richard, Van Sluis, Peter, Wolf, Stephan, Mikkelsen, Tom, Gajjar, Amar, Aldape, Kenneth, Moore, Andrew S., Taylor, Michael D., Jones, Chris, Jabado, Nada, Karajannis, Matthias A., Eils, Roland, Schlesner, Matthias, Lichter, Peter, Von Deimling, Andreas, Pfister, Stefan M., Ellison, David W., Korshunov, Andrey, and Kool, Marcel
Published: 2016

48. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

Author: Sturm, Dominik, Orr, Brent A, Toprak, Umut H, Hovestadt, Volker, Jones, David T W, Capper, David, Sill, Martin, Buchhalter, Ivo, Northcott, Paul A, Leis, Irina, Ryzhova, Marina, Koelsche, Christian, Pfaff, Elke, Allen, Sariah J, Balasubramanian, Gnanaprakash, Worst, Barbara C, Pajtler, Kristian W, Brabetz, Sebastian, Johann, Pascal David, Sahm, Felix, Reimand, Jüri, Mackay, Alan sim, Carvalho, Diana M, Remke, Marc, Phillips, Joanna J, Perry, Arie, Cowdrey, Cynthia, Drissi, Rachid, Fouladi, Maryam, Giangaspero, Felice, Łastowska, Maria, Grajkowska, Wiesława, Scheurlen, Wolfram, Pietsch, Torsten, Hagel, Christian, Gojo, Johannes, Lötsch, Daniela, Berger, Walter, Slavc, Irene, Haberler, Christine, Jouvet, Anne, Holm, Stefan, Hofer, Silvia, Prinz, Marco, Keohane, Catherine, Fried, Iris, Mawrin, Christian, Scheie, David, Mobley, Bret C, Schniederjan, Matthew J, Santi, Mariarita, Buccoliero, Anna M, Dahiya, Sonika, Kramm, Christof M, von Bueren, André O, von Hoff, Katja, Rutkowski, Stefan, Herold-Mende, Christel, Frühwald, Michael C, Milde, Till, Hasselblatt, Martin, Wesseling, Pieter, Rössler, Jochen, Schüller, Ulrich, Ebinger, Martin, Schittenhelm, Jens, Frank, Stephan, Grobholz, Rainer, Vajtai, Istvan, Hans, Volkmar, Schneppenheim, Reinhard, Zitterbart, Karel, Collins, V Peter, Aronica, Eleonora, Varlet, Pascale, Puget, Stephanie, Dufour, Christelle, Grill, Jacques, Figarella-Branger, Dominique, Wolter, Marietta, Schuhmann, Martin U, Shalaby, Tarek, Grotzer, Michael, van Meter, Timothy, Monoranu, Camelia-Maria, Felsberg, Jörg, Reifenberger, Guido, Snuderl, Matija, Forrester, Lynn Ann, Koster, Jan, Versteeg, Rogier, Volckmann, Richard, van Sluis, Peter, Wolf, Stephan, Mikkelsen, Tom, Gajjar, Amar, Aldape, Kenneth, Moore, Andrew S., Taylor, Michael D, Jones, Chris, Jabado, Nada, Karajannis, Matthias A, Eils, Roland, Schlesner, Matthias, Lichter, Peter, von Deimling, Andreas, Pfister, Stefan M, Ellison, David W, Korshunov, Andrey, Kool, Marcel, Sturm, Dominik, Orr, Brent A, Toprak, Umut H, Hovestadt, Volker, Jones, David T W, Capper, David, Sill, Martin, Buchhalter, Ivo, Northcott, Paul A, Leis, Irina, Ryzhova, Marina, Koelsche, Christian, Pfaff, Elke, Allen, Sariah J, Balasubramanian, Gnanaprakash, Worst, Barbara C, Pajtler, Kristian W, Brabetz, Sebastian, Johann, Pascal David, Sahm, Felix, Reimand, Jüri, Mackay, Alan sim, Carvalho, Diana M, Remke, Marc, Phillips, Joanna J, Perry, Arie, Cowdrey, Cynthia, Drissi, Rachid, Fouladi, Maryam, Giangaspero, Felice, Łastowska, Maria, Grajkowska, Wiesława, Scheurlen, Wolfram, Pietsch, Torsten, Hagel, Christian, Gojo, Johannes, Lötsch, Daniela, Berger, Walter, Slavc, Irene, Haberler, Christine, Jouvet, Anne, Holm, Stefan, Hofer, Silvia, Prinz, Marco, Keohane, Catherine, Fried, Iris, Mawrin, Christian, Scheie, David, Mobley, Bret C, Schniederjan, Matthew J, Santi, Mariarita, Buccoliero, Anna M, Dahiya, Sonika, Kramm, Christof M, von Bueren, André O, von Hoff, Katja, Rutkowski, Stefan, Herold-Mende, Christel, Frühwald, Michael C, Milde, Till, Hasselblatt, Martin, Wesseling, Pieter, Rössler, Jochen, Schüller, Ulrich, Ebinger, Martin, Schittenhelm, Jens, Frank, Stephan, Grobholz, Rainer, Vajtai, Istvan, Hans, Volkmar, Schneppenheim, Reinhard, Zitterbart, Karel, Collins, V Peter, Aronica, Eleonora, Varlet, Pascale, Puget, Stephanie, Dufour, Christelle, Grill, Jacques, Figarella-Branger, Dominique, Wolter, Marietta, Schuhmann, Martin U, Shalaby, Tarek, Grotzer, Michael, van Meter, Timothy, Monoranu, Camelia-Maria, Felsberg, Jörg, Reifenberger, Guido, Snuderl, Matija, Forrester, Lynn Ann, Koster, Jan, Versteeg, Rogier, Volckmann, Richard, van Sluis, Peter, Wolf, Stephan, Mikkelsen, Tom, Gajjar, Amar, Aldape, Kenneth, Moore, Andrew S., Taylor, Michael D, Jones, Chris, Jabado, Nada, Karajannis, Matthias A, Eils, Roland, Schlesner, Matthias, Lichter, Peter, von Deimling, Andreas, Pfister, Stefan M, Ellison, David W, Korshunov, Andrey, and Kool, Marcel
Abstract: Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.
Published: 2016

49. Divergent clonal selection dominates medulloblastoma at recurrence

Author: Morrissy, A. Sorana, Garzia, Livia, Shih, David J. H., Zuyderduyn, Scott, Huang, Xi, Skowron, Patryk, Remke, Marc, Cavalli, Florence M. G., Ramaswamy, Vijay, Lindsay, Patricia E., Jelveh, Salomeh, Donovan, Laura K., Wang, Xin, Luu, Betty, Zayne, Kory, Li, Yisu, Mayoh, Chelsea, Thiessen, Nina, Mercier, Eloi, Mungall, Karen L., Ma, Yusanne, Tse, Kane, Zeng, Thoma, Shumansky, Karey, Roth, Andrew J. L., Shah, Sohrab, Farooq, Hamza, Kijima, Noriyuki, Holgado, Borja L., Lee, John J. Y., Matan-Lithwick, Stuart, Liu, Jessica, Mack, Stephen C., Manno, Alex, Michealraj, K. A., Nor, Carolina, Peacock, John, Qin, Lei, Reimand, Juri, Rolider, Adi, Thompson, Yuan Y., Wu, Xiaochong, Pugh, Trevor, Ally, Adrian, Bilenky, Mikhail, Butterfield, Yaron S. N., Carlsen, Rebecca, Cheng, Young, Chuah, Eric, Corbett, Richard D., Dhalla, Noreen, He, An, Lee, Darlene, Li, Haiyan I., Long, William, Mayo, Michael, Plettner, Patrick, Qian, Jenny Q., Schein, Jacqueline E., Tam, Angela, Wong, Tina, Birol, Inanc, Zhao, Yongjun, Faria, Claudia C., Pimentel, José, Nunes, Sofia, Shalaby, Tarek, Grotzer, Michael, Pollack, Ian F., Hamilton, Ronald L., Li, Xiao-Nan, Bendel, Anne E., Fults, Daniel W., Walter, Andrew W., Kumabe, Toshihiro, Tominaga, Teiji, Collins, V. Peter, Cho, Yoon-Jae, Hoffman, Caitlin, Lyden, David, Wisoff, Jeffrey H., Garvin, James H., Stearns, Duncan S., Massimi, Luca, Schüller, Ulrich, Sterba, Jaroslav, Zitterbart, Karel, Puget, Stephanie, Ayrault, Olivier, Dunn, Sandra E., Tirapelli, Daniela P. C., Carlotti, Carlos G., Wheeler, Helen, Hallahan, Andrew R., Ingram, Wendy, Macdonald, Tobey J., Olson, Jeffrey J., Van Meir, Erwin G., Lee, Ji-Yeoun, Wang, Kyu-Chang, Kim, Seung-Ki, Cho, Byung-Kyu, Pietsch, Torsten, Fleischhack, Gudrun, Tippelt, Stephan, Ra, Young Shin, Bailey, Simon, Lindsey, Janet C., Clifford, Steven C., Eberhart, Charles G., Cooper, Michael K., Packer, Roger J., Massimino, Maura, Garre, Maria Luisa, Bartels, Ute, Tabori, Uri, Hawkins, Cynthia E., Dirks, Peter, Bouffet, Eric, Rutka, James T., Wechsler-Reya, Robert J., Weiss, William A., Collier, Lara S., Dupuy, Adam J., Korshunov, Andrey, Jones, David T. W., Kool, Marcel, Northcott, Paul A., Pfister, Stefan M., Largaespada, David A., Mungall, Andrew J., Moore, Richard A., Jabado, Nada, Bader, Gary D., Jones, Steven J. M., Malkin, David, Marra, Marco A., Taylor, Michael D., Morrissy, A. Sorana, Garzia, Livia, Shih, David J. H., Zuyderduyn, Scott, Huang, Xi, Skowron, Patryk, Remke, Marc, Cavalli, Florence M. G., Ramaswamy, Vijay, Lindsay, Patricia E., Jelveh, Salomeh, Donovan, Laura K., Wang, Xin, Luu, Betty, Zayne, Kory, Li, Yisu, Mayoh, Chelsea, Thiessen, Nina, Mercier, Eloi, Mungall, Karen L., Ma, Yusanne, Tse, Kane, Zeng, Thoma, Shumansky, Karey, Roth, Andrew J. L., Shah, Sohrab, Farooq, Hamza, Kijima, Noriyuki, Holgado, Borja L., Lee, John J. Y., Matan-Lithwick, Stuart, Liu, Jessica, Mack, Stephen C., Manno, Alex, Michealraj, K. A., Nor, Carolina, Peacock, John, Qin, Lei, Reimand, Juri, Rolider, Adi, Thompson, Yuan Y., Wu, Xiaochong, Pugh, Trevor, Ally, Adrian, Bilenky, Mikhail, Butterfield, Yaron S. N., Carlsen, Rebecca, Cheng, Young, Chuah, Eric, Corbett, Richard D., Dhalla, Noreen, He, An, Lee, Darlene, Li, Haiyan I., Long, William, Mayo, Michael, Plettner, Patrick, Qian, Jenny Q., Schein, Jacqueline E., Tam, Angela, Wong, Tina, Birol, Inanc, Zhao, Yongjun, Faria, Claudia C., Pimentel, José, Nunes, Sofia, Shalaby, Tarek, Grotzer, Michael, Pollack, Ian F., Hamilton, Ronald L., Li, Xiao-Nan, Bendel, Anne E., Fults, Daniel W., Walter, Andrew W., Kumabe, Toshihiro, Tominaga, Teiji, Collins, V. Peter, Cho, Yoon-Jae, Hoffman, Caitlin, Lyden, David, Wisoff, Jeffrey H., Garvin, James H., Stearns, Duncan S., Massimi, Luca, Schüller, Ulrich, Sterba, Jaroslav, Zitterbart, Karel, Puget, Stephanie, Ayrault, Olivier, Dunn, Sandra E., Tirapelli, Daniela P. C., Carlotti, Carlos G., Wheeler, Helen, Hallahan, Andrew R., Ingram, Wendy, Macdonald, Tobey J., Olson, Jeffrey J., Van Meir, Erwin G., Lee, Ji-Yeoun, Wang, Kyu-Chang, Kim, Seung-Ki, Cho, Byung-Kyu, Pietsch, Torsten, Fleischhack, Gudrun, Tippelt, Stephan, Ra, Young Shin, Bailey, Simon, Lindsey, Janet C., Clifford, Steven C., Eberhart, Charles G., Cooper, Michael K., Packer, Roger J., Massimino, Maura, Garre, Maria Luisa, Bartels, Ute, Tabori, Uri, Hawkins, Cynthia E., Dirks, Peter, Bouffet, Eric, Rutka, James T., Wechsler-Reya, Robert J., Weiss, William A., Collier, Lara S., Dupuy, Adam J., Korshunov, Andrey, Jones, David T. W., Kool, Marcel, Northcott, Paul A., Pfister, Stefan M., Largaespada, David A., Mungall, Andrew J., Moore, Richard A., Jabado, Nada, Bader, Gary D., Jones, Steven J. M., Malkin, David, Marra, Marco A., and Taylor, Michael D.
Abstract: The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (<12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.
Published: 2016

50. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis

Author: Thompson, Eric M, Hielscher, Thoma, Bouffet, Eric, Remke, Marc, Luu, Betty, Gururangan, Sridharan, Mclendon, Roger E, Bigner, Darell D, Lipp, Eric S, Perreault, Sebastien, Cho, Yoon-Jae, Grant, Gerald, Kim, Seung-Ki, Lee, Ji Yeoun, Rao, Amulya A Nageswara, Giannini, Caterina, Li, Kay Ka Wai, Ng, Ho-Keung, Yao, Yu, Kumabe, Toshihiro, Tominaga, Teiji, Grajkowska, Wieslawa A, Perek-Polnik, Marta, Low, David C Y, Seow, Wan Tew, Chang, Kenneth T E, Mora, Jaume, Pollack, Ian F, Hamilton, Ronald L, Leary, Sarah, Moore, Andrew S, Ingram, Wendy J, Hallahan, Andrew R, Jouvet, Anne, Fèvre-Montange, Michelle, Vasiljevic, Alexandre, Faure-Conter, Cecile, Shofuda, Tomoko, Kagawa, Naoki, Hashimoto, Naoya, Jabado, Nada, Weil, Alexander G, Gayden, Tenzin, Wataya, Takafumi, Shalaby, Tarek, Grotzer, Michael, Zitterbart, Karel, Sterba, Jaroslav, Kren, Leo, Hortobágyi, Tibor, Klekner, Almo, László, Bognár, Pócza, Tímea, Hauser, Peter, Schüller, Ulrich, Jung, Shin, Jang, Woo-Youl, French, Pim J, Kros, Johan M, van Veelen, Marie-Lise C, Massimi, Luca, Leonard, Jeffrey R, Rubin, Joshua B, Vibhakar, Rajeev, Chambless, Lola B, Cooper, Michael K, Thompson, Reid C, Faria, Claudia C, Carvalho, Alice, Nunes, Sofia, Pimentel, José, Fan, Xing, Muraszko, Karin M, López-Aguilar, Enrique, Lyden, David, Garzia, Livia, Shih, David J H, Kijima, Noriyuki, Schneider, Christian, Adamski, Jennifer, Northcott, Paul A, Kool, Marcel, Jones, David T W, Chan, Jennifer A, Nikolic, Ana, Garre, Maria Luisa, Van Meir, Erwin G, Osuka, Satoru, Olson, Jeffrey J, Jahangiri, Arman, Castro, Brandyn A, Gupta, Nalin, Weiss, William A, Moxon-Emre, Iska, Mabbott, Donald J, Lassaletta, Alvaro, Hawkins, Cynthia E, Tabori, Uri, Drake, Jame, Kulkarni, Abhaya, Dirks, Peter, Rutka, James T, Korshunov, Andrey, Pfister, Stefan M, Packer, Roger J, Ramaswamy, Vijay, Taylor, Michael D, Thompson, Eric M, Hielscher, Thoma, Bouffet, Eric, Remke, Marc, Luu, Betty, Gururangan, Sridharan, Mclendon, Roger E, Bigner, Darell D, Lipp, Eric S, Perreault, Sebastien, Cho, Yoon-Jae, Grant, Gerald, Kim, Seung-Ki, Lee, Ji Yeoun, Rao, Amulya A Nageswara, Giannini, Caterina, Li, Kay Ka Wai, Ng, Ho-Keung, Yao, Yu, Kumabe, Toshihiro, Tominaga, Teiji, Grajkowska, Wieslawa A, Perek-Polnik, Marta, Low, David C Y, Seow, Wan Tew, Chang, Kenneth T E, Mora, Jaume, Pollack, Ian F, Hamilton, Ronald L, Leary, Sarah, Moore, Andrew S, Ingram, Wendy J, Hallahan, Andrew R, Jouvet, Anne, Fèvre-Montange, Michelle, Vasiljevic, Alexandre, Faure-Conter, Cecile, Shofuda, Tomoko, Kagawa, Naoki, Hashimoto, Naoya, Jabado, Nada, Weil, Alexander G, Gayden, Tenzin, Wataya, Takafumi, Shalaby, Tarek, Grotzer, Michael, Zitterbart, Karel, Sterba, Jaroslav, Kren, Leo, Hortobágyi, Tibor, Klekner, Almo, László, Bognár, Pócza, Tímea, Hauser, Peter, Schüller, Ulrich, Jung, Shin, Jang, Woo-Youl, French, Pim J, Kros, Johan M, van Veelen, Marie-Lise C, Massimi, Luca, Leonard, Jeffrey R, Rubin, Joshua B, Vibhakar, Rajeev, Chambless, Lola B, Cooper, Michael K, Thompson, Reid C, Faria, Claudia C, Carvalho, Alice, Nunes, Sofia, Pimentel, José, Fan, Xing, Muraszko, Karin M, López-Aguilar, Enrique, Lyden, David, Garzia, Livia, Shih, David J H, Kijima, Noriyuki, Schneider, Christian, Adamski, Jennifer, Northcott, Paul A, Kool, Marcel, Jones, David T W, Chan, Jennifer A, Nikolic, Ana, Garre, Maria Luisa, Van Meir, Erwin G, Osuka, Satoru, Olson, Jeffrey J, Jahangiri, Arman, Castro, Brandyn A, Gupta, Nalin, Weiss, William A, Moxon-Emre, Iska, Mabbott, Donald J, Lassaletta, Alvaro, Hawkins, Cynthia E, Tabori, Uri, Drake, Jame, Kulkarni, Abhaya, Dirks, Peter, Rutka, James T, Korshunov, Andrey, Pfister, Stefan M, Packer, Roger J, Ramaswamy, Vijay, and Taylor, Michael D
Abstract: Background Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. Methods We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (<1·5 cm2tumour remaining), or sub-total resection (≥1·5 cm2tumour remaining). We did multivariable analyses of overall survival and progression-free survival using the variables molecular subgroup (WNT, SHH, group 4, and group 3), age (<3 vs ≥3 years old), metastatic status (metastases vs no metastases), geographical location of therapy (North America/Australia vs rest of the world), receipt of chemotherapy (yes vs no) and receipt of craniospinal irradiation (<30 Gy or >30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. Findings We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox models o
Published: 2016

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