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14 results on '"Ma, Yussanne"'

1. The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions

Author

Bolouri, Hamid, Farrar, Jason E, Triche, Timothy, Jr, Ries, Rhonda E, Lim, Emilia L, Alonzo, Todd A, Ma, Yussanne, Moore, Richard, Mungall, Andrew J, Marra, Marco A, Zhang, Jinghui, Ma, Xiaotu, Liu, Yu, Liu, Yanling, Auvil, Jaime M Guidry, Davidsen, Tanja M, Gesuwan, Patee, Hermida, Leandro C, Salhia, Bodour, Capone, Stephen, Ramsingh, Giridharan, Zwaan, Christian Michel, Noort, Sanne, Piccolo, Stephen R, Kolb, E Anders, Gamis, Alan S, Smith, Malcolm A, Gerhard, Daniela S, and Meshinchi, Soheil

Subjects
Methylation -- Comparative analysis -- Research, DNA sequencing -- Physiological aspects -- Research, Gene mutation -- Health aspects -- Research, Pediatrics -- Research, Acute myelocytic leukemia -- Genetic aspects -- Research, Biological sciences, Health
Abstract

We present the molecular landscape of pediatric acute myeloid leukemia (AML) and characterize nearly 1,000 participants in Children's Oncology Group (COG) AML trials. The COG-National Cancer Institute (NCI) TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA and microRNA sequencing and CpG methylation profiling. Validated DNA variants corresponded to diverse, infrequent mutations, with fewer than 40 genes mutated in [greater than] 2% of cases. In contrast, somatic structural variants, including new gene fusions and focal deletions of MBNL1, ZEB2 and ELF1, were disproportionately prevalent in young individuals as compared to adults. Conversely, mutations in DNMT3A and TP53, which were common in adults, were conspicuously absent from virtually all pediatric cases. New mutations in GATA2, FLT3 and CBL and recurrent mutations in MYC-ITD, NRAS, KRAS and WT1 were frequent in pediatric AML. Deletions, mutations and promoter DNA hypermethylation convergently impacted Wnt signaling, Polycomb repression, innate immune cell interactions and a cluster of zinc finger-encoding genes associated with KMT2A rearrangements. These results highlight the need for and facilitate the development of age-tailored targeted therapies for the treatment of pediatric AML., Author(s): Hamid Bolouri (corresponding author) [1]; Jason E Farrar [2]; Timothy Triche, Jr [3]; Rhonda E Ries [4]; Emilia L Lim [5]; Todd A Alonzo [6, 7]; Yussanne Ma [5]; [...]

Published
2018
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2. The whole-genome landscape of medulloblastoma subtypes

Author

Northcott, Paul A., Buchhalter, Ivo, Morrissy, A. Sorana, Hovestadt, Volker, Weischenfeldt, Joachim, Ehrenberger, Tobias, Grbner, Susanne, Segura-Wang, Maia, Zichner, Thomas, Rudneva, Vasilisa A., Warnatz, Hans-Jrg, 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, Jger, Natalie, Chavez, Lukas, Hutter, Barbara, Bieg, Matthias, Paramasivam, Nagarajan, Heinold, Michael, Gu, Zuguang, Ishaque, Naveed, Jger-Schmidt, Christina, Imbusch, Charles D., Jugold, Alke, Hbschmann, 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

Subjects
DNA sequencing -- Research, Medical research, Genomes -- Research, Medulloblastoma -- Care and treatment -- Genetic aspects -- Varieties, Environmental issues, Science and technology, Zoology and wildlife conservation
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., Author(s): Paul A. Northcott [1, 2]; Ivo Buchhalter [3, 4, 5]; A. Sorana Morrissy [6]; Volker Hovestadt [7]; Joachim Weischenfeldt [8]; Tobias Ehrenberger [9]; Susanne Grbner [1, 10]; Maia Segura-Wang [...]

Published
2017
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3. Integrated genomic and molecular characterization of cervical cancer

Author

Burk, Robert D., Chen, Zigui, Saller, Charles, Tarvin, Katherine, Carvalho, Andre L., Scapulatempo-Neto, Cristovam, Silveira, Henrique C., Fregnani, Jos H., Creighton, Chad J., Anderson, Matthew L., Castro, Patricia, Wang, Sophia S., Yau, Christina, Benz, Christopher, Robertson, A. Gordon, Mungall, Karen, Lim, Lynette, Bowlby, Reanne, Sadeghi, Sara, Brooks, Denise, Sipahimalani, Payal, Mar, Richard, Ally, Adrian, Clarke, Amanda, Mungall, Andrew J., Tam, Angela, Lee, Darlene, Chuah, Eric, Schein, Jacqueline E., Tse, Kane, Kasaian, Katayoon, Ma, Yussanne, Marra, Marco A., Mayo, Michael, Balasundaram, Miruna, Thiessen, Nina, Dhalla, Noreen, Carlsen, Rebecca, Moore, Richard A., Holt, Robert A., Jones, Steven J. M., Wong, Tina, Pantazi, Angeliki, Parfenov, Michael, Kucherlapati, Raju, Hadjipanayis, Angela, Seidman, Jonathan, Kucherlapati, Melanie, Ren, Xiaojia, Xu, Andrew W., Yang, Lixing, Park, Peter J., Lee, Semin, Rabeno, Brenda, Huelsenbeck-Dill, Lori, Borowsky, Mark, Cadungog, Mark, Iacocca, Mary, Petrelli, Nicholas, Swanson, Patricia, Ojesina, Akinyemi I., Le, Xuan, Sandusky, George, Adebamowo, Sally N., Akeredolu, Teniola, Adebamowo, Clement, Reynolds, Sheila M., Shmulevich, Ilya, Shelton, Candace, Crain, Daniel, Mallery, David, Curley, Erin, Gardner, Johanna, Penny, Robert, Morris, Scott, Shelton, Troy, Liu, Jia, Lolla, Laxmi, Chudamani, Sudha, Wu, Ye, Birrer, Michael, McLellan, Michael D., Bailey, Matthew H., Miller, Christopher A., Wyczalkowski, Matthew A., Fulton, Robert S., Fronick, Catrina C., Lu, Charles, Mardis, Elaine R., Appelbaum, Elizabeth L., Schmidt, Heather K., Fulton, Lucinda A., Cordes, Matthew G., Li, Tiandao, Ding, Li, Wilson, Richard K., Rader, Janet S., Behmaram, Behnaz, Uyar, Denise, Bradley, William, Wrangle, John, Pastore, Alessandro, Levine, Douglas A., Dao, Fanny, Gao, Jianjiong, Schultz, Nikolaus, Sander, Chris, Ladanyi, Marc, Einstein, Mark, Teeter, Randall, Benz, Stephen, Wentzensen, Nicolas, Felau, Ina, Zenklusen, Jean C., Bodelon, Clara, Demchok, John A., Yang, Liming, Sheth, Margi, Ferguson, Martin L., Tarnuzzer, Roy, Yang, Hannah, Schiffman, Mark, Zhang, Jiashan, Wang, Zhining, Davidsen, Tanja, Olaniyan, Olayinka, Hutter, Carolyn M., Sofia, Heidi J., Gordenin, Dmitry A., Chan, Kin, Roberts, Steven A., Klimczak, Leszek J., Van Waes, Carter, Chen, Zhong, Saleh, Anthony D., Cheng, Hui, Parfitt, Jeremy, Bartlett, John, Albert, Monique, Arnaout, Angel, Sekhon, Harman, Gilbert, Sebastien, Peto, Myron, Myers, Jerome, Harr, Jodi, Eckman, John, Bergsten, Julie, Tucker, Kelinda, Zach, Leigh Anne, Karlan, Beth Y., Lester, Jenny, Orsulic, Sandra, Sun, Qiang, Naresh, Rashi, Pihl, Todd, Wan, Yunhu, Zaren, Howard, Sapp, Jennifer, Miller, Judy, Drwiega, Paul, Murray, Bradley A., Zhang, Hailei, Cherniack, Andrew D., Sougnez, Carrie, Pedamallu, Chandra Sekhar, Lichtenstein, Lee, Meyerson, Matthew, Noble, Michael S., Heiman, David I., Voet, Doug, Getz, Gad, Saksena, Gordon, Kim, Jaegil, Shih, Juliann, Cho, Juok, Lawrence, Michael S., Gehlenborg, Nils, Lin, Pei, Beroukhim, Rameen, Frazer, Scott, Gabriel, Stacey B., Schumacher, Steven E., Leraas, Kristen M., Lichtenberg, Tara M., Zmuda, Erik, Bowen, Jay, Frick, Jessica, Gastier-Foster, Julie M., Wise, Lisa, Gerken, Mark, Ramirez, Nilsa C., Danilova, Ludmila, Cope, Leslie, Baylin, Stephen B., Salvesen, Helga B., Vellano, Christopher P., Ju, Zhenlin, Diao, Lixia, Zhao, Hao, Chong, Zechen, Ryan, Michael C., Martinez-Ledesma, Emmanuel, Verhaak, Roeland G., Averett Byers, Lauren, Yuan, Yuan, Chen, Ken, Ling, Shiyun, Mills, Gordon B., Lu, Yiling, Akbani, Rehan, Seth, Sahil, Liang, Han, Wang, Jing, Han, Leng, Weinstein, John N., Bristow, Christopher A., Zhang, Wei, Mahadeshwar, Harshad S., Sun, Huandong, Tang, Jiabin, Zhang, Jianhua, Song, Xingzhi, Protopopov, Alexei, Shaw, Kenna R. Mills, Chin, Lynda, Olabode, Oluwole, DiSaia, Philip, Radenbaugh, Amie, Haussler, David, Zhu, Jingchun, Stuart, Josh, Chalise, Prabhakar, Koestler, Devin, Fridley, Brooke L., Godwin, Andrew K., Madan, Rashna, Ciriello, Giovanni, Martinez, Cathleen, Higgins, Kelly, Bocklage, Therese, Auman, J. Todd, Perou, Charles M., Tan, Donghui, Parker, Joel S., Hoadley, Katherine A., Wilkerson, Matthew D., Mieczkowski, Piotr A., Skelly, Tara, Veluvolu, Umadevi, Hayes, D. Neil, Rathmell, W. Kimryn, Hoyle, Alan P., Simons, Janae V., Wu, Junyuan, Mose, Lisle E., Soloway, Matthew G., Balu, Saianand, Meng, Shaowu, Jefferys, Stuart R., Bodenheimer, Tom, Shi, Yan, Roach, Jeffrey, Thorne, Leigh B., Boice, Lori, Huang, Mei, Jones, Corbin D., Zuna, Rosemary, Walker, Joan, Gunderson, Camille, Snowbarger, Carie, Brown, David, Moxley, Katherine, Moore, Kathleen, Andrade, Kelsi, Landrum, Lisa, Mannel, Robert, McMeekin, Scott, Johnson, Starla, Nelson, Tina, Elishaev, Esther, Dhir, Rajiv, Edwards, Robert, Bhargava, Rohit, Tiezzi, Daniel G., Andrade, Jurandyr M., Noushmehr, Houtan, Gilberto Carlotti, Carlos, Jr, Tirapelli, Daniela Pretti da Cunha, Weisenberger, Daniel J., Van Den Berg, David J., Maglinte, Dennis T., Bootwalla, Moiz S., Lai, Phillip H., Triche, Timothy, Jr, Swisher, Elizabeth M., Agnew, Kathy J., Shelley, Carl Simon, Laird, Peter W., Schwarz, Julie, Grigsby, Perry, and Mutch, David

Subjects
Cervical cancer -- Genetic aspects -- Care and treatment -- Causes of, Gene mutation -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers., Author(s): The Cancer Genome Atlas Research Network; Albert Einstein College of Medicine; Robert D. Burk [1]; Zigui Chen [1]; Analytical Biological Services; Charles Saller [2]; Katherine Tarvin [2]; Barretos Cancer [...]

Published
2017
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4. Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy

Author

Lan, Xiaoyang, Jrg, David J., Cavalli, Florence M. G., Richards, Laura M., Nguyen, Long V., Vanner, Robert J., Guilhamon, Paul, Lee, Lilian, Kushida, Michelle M., Pellacani, Davide, Park, Nicole I., Coutinho, Fiona J., Whetstone, Heather, Selvadurai, Hayden J., Che, Clare, Luu, Betty, Carles, Annaick, Moksa, Michelle, Rastegar, Naghmeh, Head, Renee, Dolma, Sonam, Prinos, Panagiotis, Cusimano, Michael D., Das, Sunit, Bernstein, Mark, Arrowsmith, Cheryl H., Mungall, Andrew J., Moore, Richard A., Ma, Yussanne, Gallo, Marco, Lupien, Mathieu, Pugh, Trevor J., Taylor, Michael D., Hirst, Martin, Eaves, Connie J., Simons, Benjamin D., and Dirks, Peter B.

Subjects
Medical research, Chromosome mapping -- Research, Stem cells -- Genetic aspects, Glioblastomas -- Analysis -- Models -- Genetic aspects -- Development and progression, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Human glioblastomas harbour a subpopulation of glioblastoma stem cells that drive tumorigenesis. However, the origin of intratumoural functional heterogeneity between glioblastoma cells remains poorly understood. Here we study the clonal evolution of barcoded glioblastoma cells in an unbiased way following serial xenotransplantation to define their individual fate behaviours. Independent of an evolving mutational signature, we show that the growth of glioblastoma clones in vivo is consistent with a remarkably neutral process involving a conserved proliferative hierarchy rooted in glioblastoma stem cells. In this model, slow-cycling stem-like cells give rise to a more rapidly cycling progenitor population with extensive self-maintenance capacity, which in turn generates non-proliferative cells. We also identify rare outlier clones that deviate from these dynamics, and further show that chemotherapy facilitates the expansion of pre-existing drug-resistant glioblastoma stem cells. Finally, we show that functionally distinct glioblastoma stem cells can be separately targeted using epigenetic compounds, suggesting new avenues for glioblastoma-targeted therapy., Author(s): Xiaoyang Lan [1, 2, 3]; David J. Jrg [4, 5]; Florence M. G. Cavalli [1, 2]; Laura M. Richards [6, 7]; Long V. Nguyen [8]; Robert J. Vanner [1, [...]

Published
2017
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5. Integrated genomic characterization of oesophageal carcinoma

Author

Kim, Jihun, Bowlby, Reanne, Mungall, Andrew J., Robertson, A. Gordon, Odze, Robert D., Cherniack, Andrew D., Shih, Juliann, Pedamallu, Chandra Sekhar, Cibulskis, Carrie, Dunford, Andrew, Meier, Samuel R., Kim, Jaegil, Raphael, Benjamin J., Wu, Hsin-Ta, Wong, Alexandra M., Willis, Joseph E., Bass, Adam J., Derks, Sarah, Garman, Katherine, McCall, Shannon J., Wiznerowicz, Maciej, Pantazi, Angeliki, Parfenov, Michael, Thorsson, Vsteinn, Shmulevich, Ilya, Dhankani, Varsha, Miller, Michael, Sakai, Ryo, Wang, Kenneth, Schultz, Nikolaus, Shen, Ronglai, Arora, Arshi, Weinhold, Nils, Snchez-Vega, Francisco, Kelsen, David P., Zhang, Julia, Felau, Ina, Demchok, John, Rabkin, Charles S., Camargo, M. Constanza, Zenklusen, Jean Claude, Bowen, Jay, Leraas, Kristen, Lichtenberg, Tara M., Curtis, Christina, Seoane, Jose A., Ojesina, Akinyemi I., Beer, David G., Gulley, Margaret L., Pennathur, Arjun, Luketich, James D., Zhou, Zhongren, Weisenberger, Daniel J., Akbani, Rehan, Lee, Ju-Seog, Liu, Wenbin, Mills, Gordon B., Zhang, Wei, Reid, Brian J, Hinoue, Toshinori, Laird, Peter W., Shen, Hui, Piazuelo, M. Blanca, Schneider, Barbara G., McLellan, Michael, Taylor-Weiner, Amaro, Lawrence, Michael, Cibulskis, Kristian, Stewart, Chip, Getz, Gad, Lander, Eric, Gabriel, Stacey B., Ding, Li, McLellan, Michael D., Miller, Christopher A., Appelbaum, Elizabeth L., Cordes, Matthew G., Fronick, Catrina C., Fulton, Lucinda A., Mardis, Elaine R., Wilson, Richard K., Schmidt, Heather K., Fulton, Robert S., Ally, Adrian, Balasundaram, Miruna, Carlsen, Rebecca, Chuah, Eric, Dhalla, Noreen, Holt, Robert A., Jones, Steven J. M., Kasaian, Katayoon, Brooks, Denise, Li, Haiyan I., Ma, Yussanne, Marra, Marco A., Mayo, Michael, Moore, Richard A., Mungall, Karen L., Schein, Jacqueline E., Sipahimalani, Payal, Tam, Angela, Thiessen, Nina, Wong, Tina, Beroukhim, Rameen, Bullman, Susan, Murray, Bradley A., Saksena, Gordon, Schumacher, Steven E., Gabriel, Stacey, Meyerson, Matthew, Hadjipanayis, Angela, Kucherlapati, Raju, Ren, Xiaojia, Park, Peter J., Lee, Semin, Kucherlapati, Melanie, Yang, Lixing, Baylin, Stephen B., Hoadley, Katherine A., Bootwalla, Moiz S., Lai, Phillip H., Van Den Berg, David J., Berrios, Mario, Holbrook, Andrea, Hwang, Jun-Eul, Jang, Hee-Jin, Weinstein, John N., Lu, Yiling, Sohn, Bo Hwa, Mills, Gordon, Seth, Sahil, Protopopov, Alexei, Bristow, Christopher A., Mahadeshwar, Harshad S., Tang, Jiabin, Song, Xingzhi, Zhang, Jianhua, Cho, Juok, Defrietas, Timothy, Frazer, Scott, Gehlenborg, Nils, Heiman, David I., Lawrence, Michael S., Lin, Pei, Noble, Michael S., Voet, Doug, Zhang, Hailei, Polak, Paz, Chin, Lynda, Bernard, Brady, Iype, Lisa, Reynolds, Sheila M., Abeshouse, Adam, Armenia, Joshua, Kundra, Ritika, Ladanyi, Marc, Lehmann, Kjong-Van, Gao, Jianjiong, Sander, Chris, Chakravarty, Debyani, Zhang, Hongxin, Radenbaugh, Amie, Hegde, Apruva, Penny, Robert, Crain, Daniel, Gardner, Johanna, Curley, Erin, Mallery, David, Morris, Scott, Paulauskis, Joseph, Shelton, Troy, Shelton, Candace, Frick, Jessica, Gastier-Foster, Julie M., Gerken, Mark, Leraas, Kristen M., Ramirez, Nilsa C., Wise, Lisa, Zmuda, Erik, Tarvin, Katherine, Saller, Charles, Park, Young Soo, Button, Michael, Carvalho, Andre L., Reis, Rui Manuel, Matsushita, Marcus Medeiros, Lucchesi, Fabiano, de Oliveira, Antonio Talvane, Le, Xuan, Paklina, Oxana, Setdikova, Galiya, Lee, Jae-Hyuck, Bennett, Joseph, Iacocca, Mary, Huelsenbeck-Dill, Lori, Potapova, Olga, Voronina, Olga, Liu, Ouida, Fulidou, Victoria, Cates, Crystal, Sharp, Alexis, Behera, Madhusmitara, Force, Seth, Khuri, Fadio, Owonikoko, Taofeek, Pickens, Allan, Ramalingam, Suresh, Sica, Gabriel, Dinjens, Winand, van Nistelrooij, Anna, Wijnhoven, Bas, Sandusky, George, Stepa, Serghei, Juhl, Hartmut, Zornig, Carsten, Kwon, Sun Young, Kelsen, David, Kim, Hark Kyun, Bartlett, John, Parfitt, Jeremy, Chetty, Runjan, Darling, Gail, Knox, Jennifer, Wong, Rebecca, El-Zimaity, Haila, Liu, Geoffrey, Boussioutas, Alex, Park, Do Young, Kemp, Rafael, Carlotti, Carlos Gilberto, da Cunha Tirapelli, Daniela Pretti, Saggioro, Fabiano Pinto, Sankarankutty, Ajith Kumar, Noushmehr, Houtan, dos Santos, Jose Sebastio, Trevisan, Felipe Amstalden, Eschbacher, Jennifer, Dubina, Michael, Mozgovoy, Eugene, Carey, Frank, Chalmers, Sally, Forgie, Ian, Godwin, Andrew, Reilly, Colleen, Madan, Rashna, Naima, Zaid, Ferrer-Torres, Daysha, Vinco, Michele, Rathmell, W. Kimryn, Dhir, Rajiv, Luketich, James, Ajani, Jaffer A., Janjigian, Yelena, Tang, Laura, Cheong, Jae-Ho, Chudamani, Sudha, Liu, Jai, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Demchok, John A., Ferguson, Martin L., Shaw, Kenna R. Mills, Sheth, Margi, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Hutter, Carolyn M., Sofia, Heidi J., and Zhang, Jiashan

Subjects
DNA sequencing -- Methods, Esophageal cancer -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies., Author(s): The Cancer Genome Atlas Research Network; Analysis Working Group: Asan University; Jihun Kim [1]; BC Cancer Agency; Reanne Bowlby [2]; Andrew J. Mungall [2]; A. Gordon Robertson [2]; Brigham [...]

Published
2017
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6. Publisher Correction: The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions

Author

Bolouri, Hamid, Farrar, Jason E, Jr, Ries, Rhonda E, Lim, Emilia L, Alonzo, Todd A, and Ma, Yussanne

Subjects
Biological sciences, Health
Abstract

In the version of this article originally published, the color key in Fig. 1a was wrong. In the Cytogenetics key, the box over t(8;21) originally was green. It should have been red, matching the color of the sections of the pie graphs below the key that were labeled with 15% and 19%., Author(s): Hamid Bolouri [sup.1] , Jason E Farrar [sup.2] , Timothy Triche [sup.3] [sup.17] , Rhonda E Ries [sup.4] , Emilia L Lim [sup.5] , Todd A Alonzo [sup.6] [sup.7] [...]

Published
2019
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7. 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

8. Erratum: The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions

Author

Bolouri, Hamid, Farrar, Jason E, Triche, Timothy, Jr, Ries, Rhonda E, Lim, Emilia L, Alonzo, Todd A, Ma, Yussanne, Moore, Richard, Mungall, Andrew J, Marra, Marco A, Zhang, Jinghui, Ma, Xiaotu, Liu, Yu, Liu, Yanling, Auvil, Jaime M Guidry, Davidsen, Tanja M, Gesuwan, Patee, Hermida, Leandro C, Salhia, Bodour, Capone, Stephen, Ramsingh, Giridharan, Zwaan, Christian Michel, Noort, Sanne, Piccolo, Stephen R, Kolb, E Anders, Gamis, Alan S, Smith, Malcolm A, Gerhard, Daniela S, and Meshinchi, Soheil

Subjects
Biological sciences, Health
Abstract

Author(s): Hamid Bolouri; Jason E Farrar; Timothy Triche, Jr; Rhonda E Ries; Emilia L Lim; Todd A Alonzo; Yussanne Ma; Richard Moore; Andrew J Mungall; Marco A Marra; Jinghui Zhang; [...]

Published
2018
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9. A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3)

Author

Enciso-Mora, Victor, Broderick, Peter, Ma, Yussanne, Jarrett, Ruth F., Hjalgrim, Henrik, Hemminki, Kari, van den Berg, Anke, Olver, Bianca, Lloyd, Amy, Dobbins, Sara E., Lightfoot, Tracy, van Leeuwen, Flora E., Foersti, Asta, Diepstra, Arjan, Broeks, Annegien, Vijayakrishnan, Jayaram, Shield, Lesley, Lake, Annette, Montgomery, Dorothy, Roman, Eve, Engert, Andreas, von Strandmann, Elke Pogge, Reiners, Katrin S., Nolte, Ilja M., Smedby, Karin E., Adami, Hans-Olov, Russell, Nicola S., Glimelius, Bengt, Hamilton-Dutoit, Stephen, de Bruin, Marieke, Ryder, Lars P., Molin, Daniel, Sorensen, Karina Meden, Chang, Ellen T., Taylor, Malcolm, Cooke, Rosie, Hofstra, Robert, Westers, Helga, van Wezel, Tom, van Eijk, Ronald, Ashworth, Alan, Rostgaard, Klaus, Melbye, Mads, Swerdlow, Anthony J., Houlston, Richard S., Enciso-Mora, Victor, Broderick, Peter, Ma, Yussanne, Jarrett, Ruth F., Hjalgrim, Henrik, Hemminki, Kari, van den Berg, Anke, Olver, Bianca, Lloyd, Amy, Dobbins, Sara E., Lightfoot, Tracy, van Leeuwen, Flora E., Foersti, Asta, Diepstra, Arjan, Broeks, Annegien, Vijayakrishnan, Jayaram, Shield, Lesley, Lake, Annette, Montgomery, Dorothy, Roman, Eve, Engert, Andreas, von Strandmann, Elke Pogge, Reiners, Katrin S., Nolte, Ilja M., Smedby, Karin E., Adami, Hans-Olov, Russell, Nicola S., Glimelius, Bengt, Hamilton-Dutoit, Stephen, de Bruin, Marieke, Ryder, Lars P., Molin, Daniel, Sorensen, Karina Meden, Chang, Ellen T., Taylor, Malcolm, Cooke, Rosie, Hofstra, Robert, Westers, Helga, van Wezel, Tom, van Eijk, Ronald, Ashworth, Alan, Rostgaard, Klaus, Melbye, Mads, Swerdlow, Anthony J., and Houlston, Richard S.

Abstract

To identify susceptibility loci for classical Hodgkin's lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 x 10(-8)), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 x 10(-13)) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 x 10(-8)). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 x 10(-50)). These data provide new insight into the pathogenesis of cHL.

Published
2010

10. Retraction Note: Tumor necrosis factor overcomes immune evasion in p53-mutant medulloblastoma.

Author

Garancher A, Suzuki H, Haricharan S, Chau LQ, Masihi MB, Rusert JM, Norris PS, Carrette F, Romero MM, Morrissy SA, Skowron P, Cavalli FMG, Farooq H, Ramaswamy V, Jones SJM, Moore RA, Mungall AJ, Ma Y, Thiessen N, Li Y, Morcavallo A, Qi L, Kogiso M, Du Y, Baxter P, Henderson JJ, Crawford JR, Levy ML, Olson JM, Cho YJ, Deshpande AJ, Li XN, Chesler L, Marra MA, Wajant H, Becher OJ, Bradley LM, Ware CF, Taylor MD, and Wechsler-Reya RJ

Published
2022
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11. Tumor necrosis factor overcomes immune evasion in p53-mutant medulloblastoma.

Author

Garancher A, Suzuki H, Haricharan S, Chau LQ, Masihi MB, Rusert JM, Norris PS, Carrette F, Romero MM, Morrissy SA, Skowron P, Cavalli FMG, Farooq H, Ramaswamy V, Jones SJM, Moore RA, Mungall AJ, Ma Y, Thiessen N, Li Y, Morcavallo A, Qi L, Kogiso M, Du Y, Baxter P, Henderson JJ, Crawford JR, Levy ML, Olson JM, Cho YJ, Deshpande AJ, Li XN, Chesler L, Marra MA, Wajant H, Becher OJ, Bradley LM, Ware CF, Taylor MD, and Wechsler-Reya RJ

Subjects
Animals, Cerebellar Neoplasms genetics, Cerebellar Neoplasms metabolism, Medulloblastoma genetics, Medulloblastoma metabolism, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, SCID, Neoplasm Transplantation, Tumor Necrosis Factor-alpha metabolism, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Cerebellar Neoplasms immunology, Medulloblastoma immunology, Tumor Escape immunology, Tumor Necrosis Factor-alpha immunology, Tumor Suppressor Protein p53 immunology
Abstract

Many immunotherapies act by enhancing the ability of cytotoxic T cells to kill tumor cells. Killing depends on T cell recognition of antigens presented by class I major histocompatibility complex (MHC-I) proteins on tumor cells. In this study, we showed that medulloblastomas lacking the p53 tumor suppressor do not express surface MHC-I and are therefore resistant to immune rejection. Mechanistically, this is because p53 regulates expression of the peptide transporter Tap1 and the aminopeptidase Erap1, which are required for MHC-I trafficking to the cell surface. In vitro, tumor necrosis factor (TNF) or lymphotoxin-β receptor agonist can rescue expression of Erap1, Tap1 and MHC-I on p53-mutant tumor cells. In vivo, low doses of TNF prolong survival and synergize with immune checkpoint inhibitors to promote tumor rejection. These studies identified p53 as a key regulator of immune evasion and suggest that TNF could be used to enhance sensitivity of tumors to immunotherapy.

Published
2020
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12. Pan-cancer analysis of advanced patient tumors reveals interactions between therapy and genomic landscapes.

Author

Pleasance E, Titmuss E, Williamson L, Kwan H, Culibrk L, Zhao EY, Dixon K, Fan K, Bowlby R, Jones MR, Shen Y, Grewal JK, Ashkani J, Wee K, Grisdale CJ, Thibodeau ML, Bozoky Z, Pearson H, Majounie E, Vira T, Shenwai R, Mungall KL, Chuah E, Davies A, Warren M, Reisle C, Bonakdar M, Taylor GA, Csizmok V, Chan SK, Zong Z, Bilobram S, Muhammadzadeh A, D'Souza D, Corbett RD, MacMillan D, Carreira M, Choo C, Bleile D, Sadeghi S, Zhang W, Wong T, Cheng D, Brown SD, Holt RA, Moore RA, Mungall AJ, Zhao Y, Nelson J, Fok A, Ma Y, Lee MKC, Lavoie JM, Mendis S, Karasinska JM, Deol B, Fisic A, Schaeffer DF, Yip S, Schrader K, Regier DA, Weymann D, Chia S, Gelmon K, Tinker A, Sun S, Lim H, Renouf DJ, Laskin J, Jones SJM, and Marra MA

Subjects
Humans, Neoplasms drug therapy
Abstract

Advanced and metastatic tumors with complex treatment histories drive cancer mortality. Here we describe the POG570 cohort, a comprehensive whole-genome, transcriptome and clinical dataset, amenable for exploration of the impacts of therapies on genomic landscapes. Previous exposure to DNA-damaging chemotherapies and mutations affecting DNA repair genes, including POLQ and genes encoding Polζ, were associated with genome-wide, therapy-induced mutagenesis. Exposure to platinum therapies coincided with signatures SBS31 and DSB5 and, when combined with DNA synthesis inhibitors, signature SBS17b. Alterations in ESR1, EGFR, CTNNB1, FGFR1, VEGFA and DPYD were consistent with drug resistance and sensitivity. Recurrent noncoding events were found in regulatory region hotspots of genes including TERT, PLEKHS1, AP2A1 and ADGRG6. Mutation burden and immune signatures corresponded with overall survival and response to immunotherapy. Our data offer a rich resource for investigation of advanced cancers and interpretation of whole-genome and transcriptome sequencing in the context of a cancer clinic., (© 2020. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Published
2020
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13. The genetic basis and cell of origin of mixed phenotype acute leukaemia.

Author

Alexander TB, Gu Z, Iacobucci I, Dickerson K, Choi JK, Xu B, Payne-Turner D, Yoshihara H, Loh ML, Horan J, Buldini B, Basso G, Elitzur S, de Haas V, Zwaan CM, Yeoh A, Reinhardt D, Tomizawa D, Kiyokawa N, Lammens T, De Moerloose B, Catchpoole D, Hori H, Moorman A, Moore AS, Hrusak O, Meshinchi S, Orgel E, Devidas M, Borowitz M, Wood B, Heerema NA, Carrol A, Yang YL, Smith MA, Davidsen TM, Hermida LC, Gesuwan P, Marra MA, Ma Y, Mungall AJ, Moore RA, Jones SJM, Valentine M, Janke LJ, Rubnitz JE, Pui CH, Ding L, Liu Y, Zhang J, Nichols KE, Downing JR, Cao X, Shi L, Pounds S, Newman S, Pei D, Guidry Auvil JM, Gerhard DS, Hunger SP, Inaba H, and Mullighan CG

Subjects
Cell Lineage genetics, DNA Mutational Analysis, Female, Genetic Variation genetics, Genome, Human genetics, Genomics, Humans, Immunophenotyping, Leukemia, Biphenotypic, Acute classification, Male, Models, Genetic, Mutation genetics, Neoplastic Stem Cells immunology, Neoplastic Stem Cells metabolism, Neoplastic Stem Cells pathology, Phenotype, Trans-Activators genetics, Leukemia, Biphenotypic, Acute genetics, Leukemia, Biphenotypic, Acute pathology
Abstract

Mixed phenotype acute leukaemia (MPAL) is a high-risk subtype of leukaemia with myeloid and lymphoid features, limited genetic characterization, and a lack of consensus regarding appropriate therapy. Here we show that the two principal subtypes of MPAL, T/myeloid (T/M) and B/myeloid (B/M), are genetically distinct. Rearrangement of ZNF384 is common in B/M MPAL, and biallelic WT1 alterations are common in T/M MPAL, which shares genomic features with early T-cell precursor acute lymphoblastic leukaemia. We show that the intratumoral immunophenotypic heterogeneity characteristic of MPAL is independent of somatic genetic variation, that founding lesions arise in primitive haematopoietic progenitors, and that individual phenotypic subpopulations can reconstitute the immunophenotypic diversity in vivo. These findings indicate that the cell of origin and founding lesions, rather than an accumulation of distinct genomic alterations, prime tumour cells for lineage promiscuity. Moreover, these findings position MPAL in the spectrum of immature leukaemias and provide a genetically informed framework for future clinical trials of potential treatments for MPAL.

Published
2018
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14. A somatic reference standard for cancer genome sequencing.

Author

Craig DW, Nasser S, Corbett R, Chan SK, Murray L, Legendre C, Tembe W, Adkins J, Kim N, Wong S, Baker A, Enriquez D, Pond S, Pleasance E, Mungall AJ, Moore RA, McDaniel T, Ma Y, Jones SJ, Marra MA, Carpten JD, and Liang WS

Subjects
Cell Line, Tumor, Datasets as Topic, Genetic Variation, Humans, Meta-Analysis as Topic, Reference Standards, Genome, Genomics methods, Genomics standards, High-Throughput Nucleotide Sequencing, Neoplasms genetics
Abstract

Large-scale multiplexed identification of somatic alterations in cancer has become feasible with next generation sequencing (NGS). However, calibration of NGS somatic analysis tools has been hampered by a lack of tumor/normal reference standards. We thus performed paired PCR-free whole genome sequencing of a matched metastatic melanoma cell line (COLO829) and normal across three lineages and across separate institutions, with independent library preparations, sequencing, and analysis. We generated mean mapped coverages of 99X for COLO829 and 103X for the paired normal across three institutions. Results were combined with previously generated data allowing for comparison to a fourth lineage on earlier NGS technology. Aggregate variant detection led to the identification of consensus variants, including key events that represent hallmark mutation types including amplified BRAF V600E, a CDK2NA small deletion, a 12 kb PTEN deletion, and a dinucleotide TERT promoter substitution. Overall, common events include >35,000 point mutations, 446 small insertion/deletions, and >6,000 genes affected by copy number changes. We present this reference to the community as an initial standard for enabling quantitative evaluation of somatic mutation pipelines across institutions.

Published
2016
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