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16 results on '"Murray, Bradley"'

1. Erratum: Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles (Cell Reports (2017) 18(11) (2780–2794) (S2211124717302140) (10.1016/j.celrep.2017.02.033))

Author

Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A. Gordon, Hinoue, Toshinori, Hoadley, Katherine A., Gibb, Ewan A., Roszik, Jason, Covington, Kyle R., Wu, Chia-Chin, Shinbrot, Eve, Stransky, Nicolas, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I., Hess, Julian M., Auman, J. Todd, Rhie, Suhn K., Bowlby, Reanne, Borad, Mitesh J., Akbani, Rehan, Allotey, Loretta K., Ally, Adrian, Alvaro, Domenico, Andersen, Jesper B., Appelbaum, Elizabeth L., Arora, Arshi, Balasundaram, Miruna, Balu, Saianand, Bardeesy, Nabeel, Bathe, Oliver F., Baylin, Stephen B., Beroukhim, Rameen, Berrios, Mario, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S., Bowen, Jay, Bragazzi, Maria Consiglia, Brooks, Denise, Cardinale, Vincenzo, Carlsen, Rebecca, Carpino, Guido, Carvalho, Andre L., Chaiteerakij, Roongruedee, Chandan, Vishal C., Cherniack, Andrew D., Chin, Lynda, Cho, Juok, Choe, Gina, Chuah, Eric, Chudamani, Sudha, Cibulskis, Carrie, Cordes, Matthew G., Crain, Daniel, Curley, Erin, De Rose, Agostino Maria, Defreitas, Timothy, Demchok, John A., Deshpande, Vikram, Dhalla, Noreen, Ding, Li, Evason, Kimberley, Felau, Ina, Ferguson, Martin L., Foo, Wai Chin, Franchitto, Antonio, Frazer, Scott, Fronick, Catrina C., Fulton, Lucinda A., Fulton, Robert S., Gabriel, Stacey B., Gardner, Johanna, Gastier-Foster, Julie M., Gaudio, Eugenio, Gehlenborg, Nils, Genovese, Giannicola, Gerken, Mark, Getz, Gad, Giama, Nasra H., Gibbs, Richard A., Giuliante, Felice, Grazi, Gian Luca, Hayes, D. Neil, Hegde, Apurva M., Heiman, David I., Holbrook, Andrea, Holt, Robert A., Hoyle, Alan P., Huang, Mei, Hutter, Carolyn M., Jefferys, Stuart R., Jones, Steven J. M., Jones, Corbin D., Kasaian, Katayoon, Kelley, Robin K., Kim, Jaegil, Kleiner, David E., Kocher, Jean-Pierre A., Kwong, Lawrence N., Lai, Phillip H., Laird, Peter W., Lawrence, Michael S., Leraas, Kristen M., Lichtenberg, Tara M., Lin, Pei, Liu, Wenbin, Liu, Jia, Lolla, Laxmi, Lu, Yiling, Ma, Yussanne, Mallery, David, Mardis, Elaine R., Marra, Marco A., Matsushita, Marcus M., Mayo, Michael, McLellan, Michael D., McRee, Autumn J., Meier, Sam, Meng, Shaowu, Meyerson, Matthew, Mieczkowski, Piotr A., Miller, Christopher A., Mills, Gordon B., Moore, Richard A., Morris, Scott, Mose, Lisle E., Moser, Catherine D., Mounajjed, Taofic, Mungall, Andrew J., Mungall, Karen, Murray, Bradley A., Naresh, Rashi, Noble, Michael S., O'Brien, Daniel R., Parker, Joel S., Patel, Tushar C., Paulauskis, Joseph, Penny, Robert, Perou, Charles M., Perou, Amy H., Pihl, Todd, Radenbaugh, Amie J., Ramirez, Nilsa C., Rathmell, W. Kimryn, Roach, Jeffrey, Roberts, Lewis R., Saksena, Gordon, Sander, Chris, Schein, Jacqueline E., Schmidt, Heather K., Schumacher, Steven E., Shelton, Candace, Shelton, Troy, Shen, Ronglai, Sheth, Margi, Shi, Yan, Shroff, Rachna, Simons, Janae V., Sipahimalani, Payal, Skelly, Tara, Sofia, Heidi J., Soloway, Matthew G., Stoppler, Hubert, Stuart, Josh, Sun, Qiang, Tam, Angela, Tan, Donghui, Tarnuzzer, Roy, Thiessen, Nina, Thorne, Leigh B., Torbenson, Michael S., Van Den Berg, David J., Veluvolu, Umadevi, Verhaak, Roel G. W., Voet, Doug, Wan, Yunhu, Wang, Zhining, Weinstein, John N., Weisenberger, Daniel J., Wheeler, David A., Wilson, Richard K., Wise, Lisa, Wong, Tina, Wu, Ye, Xi, Liu, Yang, Liming, Zenklusen, Jean C., Zhang, Hailei, Zhang, Jiashan (Julia), Zmuda, Erik, Zhu, Andrew X., Stuart, Josh M., Farshidfar, Farshad, Zheng, Siyuan, Gingras, Marie-Claude, Newton, Yulia, Shih, Juliann, Robertson, A. Gordon, Hinoue, Toshinori, Hoadley, Katherine A., Gibb, Ewan A., Roszik, Jason, Covington, Kyle R., Chia-Chin, Wu, Shinbrot, Eve, Stransky, Nicola, Hegde, Apurva, Yang, Ju Dong, Reznik, Ed, Sadeghi, Sara, Pedamallu, Chandra Sekhar, Ojesina, Akinyemi I., Hess, Julian M., Auman, J. Todd, Rhie, Suhn K., Bowlby, Reanne, Borad, Mitesh J., Akbani, Rehan, Allotey, Loretta K., Ally, Adrian, Alvaro, Domenico, Andersen, Jesper B., Appelbaum, Elizabeth L., Arora, Arshi, Balasundaram, Miruna, Balu, Saianand, Bardeesy, Nabeel, Bathe, Oliver F., Baylin, Stephen B., Beroukhim, Rameen, Berrios, Mario, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S., Bowen, Jay, Bragazzi, Maria Consiglia, Brooks, Denise, Cardinale, Vincenzo, Carlsen, Rebecca, Guido, Carpino, Carvalho, Andre L., Chaiteerakij, Roongruedee, Chandan, Vishal C., Cherniack, Andrew D., Chin, Lynda, Cho, Juok, Choe, Gina, Chuah, Eric, Chudamani, Sudha, Cibulskis, Carrie, Cordes, Matthew G., Crain, Daniel, Curley, Erin, De Rose, Agostino Maria, Defreitas, Timothy, Demchok, John A., Deshpande, Vikram, Dhalla, Noreen, Ding, Li, Evason, Kimberley, Felau, Ina, Ferguson, Martin L., Foo, Wai Chin, Franchitto, Antonio, Frazer, Scott, Fronick, Catrina C., Fulton, Lucinda A., Fulton, Robert S., Gabriel, Stacey B., Gardner, Johanna, Gastier-Foster, Julie M., Gaudio, Eugenio, Gehlenborg, Nil, Genovese, Giannicola, Gerken, Mark, Getz, Gad, Giama, Nasra H., Gibbs, Richard A., Giuliante, Felice, Grazi, Gian Luca, Hayes, D. Neil, Hegde, Apurva M., Heiman, David I., Holbrook, Andrea, Holt, Robert A., Hoyle, Alan P., Huang, Mei, Hutter, Carolyn M., Jefferys, Stuart R., Jones, Steven J. M., Jones, Corbin D., Kasaian, Katayoon, Kelley, Robin K., Kim, Jaegil, Kleiner, David E., Kocher, Jean-Pierre A., Kwong, Lawrence N., Lai, Phillip H., Laird, Peter W., Lawrence, Michael S., Leraas, Kristen M., Lichtenberg, Tara M., Lin, Pei, Liu, Wenbin, Liu, Jia, Lolla, Laxmi, Yiling, Lu, Yussanne, Ma, Mallery, David, Mardis, Elaine R., Marra, Marco A., Matsushita, Marcus M., Mayo, Michael, Mclellan, Michael D., Mcree, Autumn J., Meier, Sam, Meng, Shaowu, Meyerson, Matthew, Mieczkowski, Piotr A., Miller, Christopher A., Mills, Gordon B., Moore, Richard A., Morris, Scott, Mose, Lisle E., Moser, Catherine D., Mounajjed, Taofic, Mungall, Andrew J., Mungall, Karen, Murray, Bradley A., Naresh, Rashi, Noble, Michael S., O'Brien, Daniel R., Parker, Joel S., Patel, Tushar C., Paulauskis, Joseph, Penny, Robert, Perou, Charles M., Perou, Amy H., Pihl, Todd, Radenbaugh, Amie J., Ramirez, Nilsa C., Rathmell, W. Kimryn, Roach, Jeffrey, Roberts, Lewis R., Saksena, Gordon, Sander, Chri, Schein, Jacqueline E., Schmidt, Heather K., Schumacher, Steven E., Shelton, Candace, Shelton, Troy, Shen, Ronglai, Sheth, Margi, Shi, Yan, Shroff, Rachna, Simons, Janae V., Sipahimalani, Payal, Skelly, Tara, Sofia, Heidi J., Soloway, Matthew G., Stoppler, Hubert, Stuart, Josh, Sun, Qiang, Tam, Angela, Tan, Donghui, Tarnuzzer, Roy, Thiessen, Nina, Thorne, Leigh B., Torbenson, Michael S., Van Den Berg, David J., Veluvolu, Umadevi, Verhaak, Roel G. W., Voet, Doug, Wan, Yunhu, Wang, Zhining, Weinstein, John N., Weisenberger, Daniel J., Wheeler, David A., Wilson, Richard K., Wise, Lisa, Wong, Tina, Ye, Wu, Liu, Xi, Yang, Liming, Zenklusen, Jean C., Zhang, Hailei, Zhang, Jiashan (Julia), Zmuda, Erik, Zhu, Andrew X., and Stuart, Josh M.

Subjects
Genetics and Molecular Biology (all), Biochemistry, Genetics and Molecular Biology (all), Biochemistry
Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

Published
2017

2. A reanalysis of Schaefer et al. does not indicate extensive CRISPR/Cas9 mediated off-target editing events

Author

Murray Bradley Andrew, Reynald Lescarbeau, Nessan Bermingham, and Thomas M. Barnes

Subjects
Genetics, 0303 health sciences, Zygote, Cas9, Strain (biology), Burden of proof, Genomics, Biology, 03 medical and health sciences, 0302 clinical medicine, Variation (linguistics), Genetic variation, CRISPR, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

Recently Schaefer et al. (1) reported the presence of more than a thousand genomic differences between mice that had been edited with S. pyogenes Cas9 at the zygote stage, and a control mouse of the same strain. Given the overlap of genomic differences between the two edited mice that were not found in the control mouse, the authors concluded that these differences arose from a Cas9-dependent activity. We feel that this conclusion is inappropriate, for three key reasons: 1) there was incomplete analysis of the genetic variation; 2) there was no consideration that the variation is naturally arising in these animals; and 3) the inferred behavior of Cas9 lies outside of its understood mechanism of action. Attribution to Cas9 activity should require a burden of proof, that we believe has not been met.

Published
2017
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3. Integrated Molecular Characterization of Uterine Carcinosarcoma

Author

Cherniack, Andrew D, Shen, Hui, Walter, Vonn, Stewart, Chip, Murray, Bradley A, Bowlby, Reanne, Hu, Xin, Ling, Shiyun, Soslow, Robert A, Broaddus, Russell R, Zuna, Rosemary E, Robertson, Gordon, Laird, Peter W, Kucherlapati, Raju, Mills, Gordon B, Cancer Genome Atlas Research Network, Weinstein, John N, Zhang, Jiashan, Akbani, Rehan, and Levine, Douglas A

Subjects
Epithelial-Mesenchymal Transition, DNA Copy Number Variations, translational science, Oncology and Carcinogenesis, The Cancer Genome Atlas, Cancer Genome Atlas Research Network, gynecologic oncology, uterine carcinosarcoma, Carcinosarcoma, Genetics, Humans, 2.1 Biological and endogenous factors, Oncology & Carcinogenesis, Aetiology, Cancer, Human Genome, EMT, Neurosciences, TGGA, Uterine Neoplasms, Mutation, endometrial cancer, UCS, Female, gynecologic cancer, epithelial-to-mesenchymal transition, Biotechnology
Abstract

We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified.

Published
2017

4. Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma

Author

Fishbein, Lauren, Leshchiner, Ignaty, Walter, Vonn, Danilova, Ludmila, Robertson, A Gordon, Johnson, Amy R, Lichtenberg, Tara M, Murray, Bradley A, Ghayee, Hans K, Else, Tobias, Ling, Shiyun, Jefferys, Stuart R, de Cubas, Aguirre A, Wenz, Brandon, Korpershoek, Esther, Amelio, Antonio L, Makowski, Liza, Rathmell, W Kimryn, Gimenez-Roqueplo, Anne-Paule, Giordano, Thomas J, Asa, Sylvia L, Tischler, Arthur S, Cancer Genome Atlas Research Network, Pacak, Karel, Nathanson, Katherine L, and Wilkerson, Matthew D

Subjects
Adult, Male, molecular profiling, Oncology and Carcinogenesis, Cancer Genome Atlas Research Network, Pheochromocytoma, Paraganglioma, 80 and over, genomics, Genetics, Humans, metastasis, 2.1 Biological and endogenous factors, Oncology & Carcinogenesis, Aetiology, Aged, Proto-Oncogene Proteins c-ret, Neurosciences, RNA-Binding Proteins, Nuclear Proteins, sequencing, Middle Aged, TCGA, DNA-Binding Proteins, expression subtypes, CSDE1, Good Health and Well Being, Mutation, Trans-Activators, Female, Gene Fusion, Pol1 Transcription Initiation Complex Proteins, MAML3, Transcription Factors
Abstract

We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine.

Published
2017

5. Integrated Molecular Characterization of Uterine Carcinosarcoma

Author

Kim, Jaegil, Shen, Hui, Hoffmann, Robert, Zhang, Wei, Tam, Angela, Jones, Steven J.M., Zhang, Jiashan, Walter, Vonn, David, Mutch, Wang, Chen, Weisenberger, Daniel J., Cherniack, Andrew D., Weinstein, John N., Dowdy, Sean, Soloway, Matthew G., Ling, Shiyun, Akbani, Rehan, Salvesen, Helga B., Gupta, Manaswi, Sougnez, Carrie, Jones, Corbin D., Bodenheimer, Tom, Verhaak, Roel G.W., Robertson, A. Gordon, Yang, Liming, Dhalla, Noreen, Getz, Gad, Leshchiner, Ignaty, Wong, Tina, Roach, Jeffrey, Zmuda, Erik, Laird, Peter W., Lai, Phillip H., Lawrence, Michael S., Zenklusen, Jean C., Haussler, David, Stewart, Chip, Tan, Donghui, Mungall, Andrew J., Felau, Ina, Naresh, Rashi, Thiessen, Nina, Olvera, Narciso, Schein, Jacqueline E., Liu, Jia, Brooks, Denise, Hoadley, Katherine A., Mieczkowski, Piotr A., Jefferys, Stuart R., Kandoth, Cyriac, Wu, Ye, Ramirez, Nilsa C., Rathmell, W. Kimryn, Winterhoff, Boris, Wise, Lisa, Ferguson, Martin L., Kanchi, Rupa S., Gastier-Foster, Julie M., Heiman, David I., Lander, Eric, Frazer, Scott, Marra, Marco A., Holt, Robert A., Hess, Julian, Noble, Michael S., Chudamani, Sudha, Lin, Pei, Carlsen, Rebecca, Baylin, Stephen B., Balu, Saianand, Broaddus, Russell R., Cibulskis, Kristian, Chuah, Eric, Shi, Yan, Shih, Juliann, Bogomolniy, Faina, Zhang, Hailei, Sofia, Heidi J., Sipahimalani, Payal, Zuna, Rosemary E., Hutter, Carolyn M., Levine, Douglas A., Radenbaugh, Amie J., von Bismarck, Amanda, Maglinte, Dennis T., Soslow, Robert A., Saksena, Gordon, Mayo, Michael, Auman, J. Todd, Kucherlapati, Raju, Huang, Mei, Tse, Kane, Wang, Zhining, Wan, Yunhu, Kasaian, Katayoon, Ally, Adrian, Bowlby, Reanne, Gerken, Mark, Tseng, Jill, Cline, Melissa, Veluvolu, Umadevi, Perou, Amy H., Mose, Lisle E., Skelly, Tara, Meng, Shaowu, Leraas, Kristen M., Zhu, Jing-chun, Meyerson, Matthew, Pihl, Todd, Beroukhim, Rameen, Demchok, John A., Dao, Fanny, Tarnuzzer, Roy, Lichtenberg, Tara M., Frick, Jessica, Sheth, Margi, Bowen, Jay, Zhang, Jiashan (Julia), Hoyle, Alan P., Hu, Xin, Voet, Doug, Mills, Gordon B., Hayes, D. Neil, Liu, Yuexin, Broaddus, Russell, Lee, Darlene, Kerr, Sarah, Lolla, Laxmi, Wilkerson, Matthew D., Moore, Richard A., Lu, Yiling, Bootwalla, Moiz S., Cho, Juok, Boice, Lori, Sun, Charlie, Thorne, Leigh B., Ma, Yussanne, Schumacher, Steven E., Balasundaram, Miruna, Parker, Joel S., Sadeghi, Sara, Robertson, Gordon, Liu, Wenbin, Perou, Charles M., Gehlenborg, Nils, Simons, Janae V., Murray, Bradley A., Mungall, Karen, Gabriel, Stacey, and Van Den Berg, David J.

Abstract

SummaryWe performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified.

Published
2017
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6. Comprehensive molecular characterization of gastric adenocarcinoma

Author

Bass, Adam J., Thorsson, Vesteinn, Shmulevich, Ilya, Reynolds, Sheila M., Miller, Michael, Bernard, Brady, Hinoue, Toshinori, Laird, Peter W., Curtis, Christina, Shen, Hui, Weisenberger, Daniel J., Schultz, Nikolaus, Shen, Ronglai, Weinhold, Nils, Kelsen, David P., Bowlby, Reanne, Chu, Andy, Kasaian, Katayoon, Mungall, Andrew J., Robertson, A. Gordon, Sipahimalani, Payal, Cherniack, Andrew, Getz, Gad, Liu, Yingchun, Noble, Michael S., Pedamallu, Chandra, Sougnez, Carrie, Taylor-Weiner, Amaro, Akbani, Rehan, Lee, Ju-Seog, Liu, Wenbin, Mills, Gordon B., Yang, Da, Zhang, Wei, Pantazi, Angeliki, Parfenov, Michael, Gulley, Margaret, Piazuelo, M. Blanca, Schneider, Barbara G., Kim, Jihun, Boussioutas, Alex, Sheth, Margi, Demchok, John A., Rabkin, Charles S., Willis, Joseph E., Ng, Sam, Garman, Katherine, Beer, David G., Pennathur, Arjun, Raphael, Benjamin J., Wu, Hsin-Ta, Odze, Robert, Kim, Hark K., Bowen, Jay, Leraas, Kristen M., Lichtenberg, Tara M., Weaver, Stephanie, McLellan, Michael, Wiznerowicz, Maciej, Sakai, Ryo, Lawrence, Michael S., Cibulskis, Kristian, Lichtenstein, Lee, Fisher, Sheila, Gabriel, Stacey B., Lander, Eric S., Ding, Li, Niu, Beifang, Ally, Adrian, Balasundaram, Miruna, Birol, Inanc, Brooks, Denise, Butterfield, Yaron S. N., Carlsen, Rebecca, Chu, Justin, Chuah, Eric, Chun, Hye-Jung E., Clarke, Amanda, Dhalla, Noreen, Guin, Ranabir, Holt, Robert A., Jones, Steven J.M., Lee, Darlene, Li, Haiyan A., Lim, Emilia, Ma, Yussanne, Marra, Marco A., Mayo, Michael, Moore, Richard A., Mungall, Karen L., Nip, Ka Ming, Schein, Jacqueline E., Tam, Angela, Thiessen, Nina, Beroukhim, Rameen, Carter, Scott L., Cherniack, Andrew D., Cho, Juok, DiCara, Daniel, Frazer, Scott, Gehlenborg, Nils, Heiman, David I., Jung, Joonil, Kim, Jaegil, Lin, Pei, Meyerson, Matthew, Ojesina, Akinyemi I., Pedamallu, Chandra Sekhar, Saksena, Gordon, Schumacher, Steven E., Stojanov, Petar, Tabak, Barbara, Voet, Doug, Rosenberg, Mara, Zack, Travis I., Zhang, Hailei, Zou, Lihua, Protopopov, Alexei, Santoso, Netty, Lee, Semin, Zhang, Jianhua, Mahadeshwar, Harshad S., Tang, Jiabin, Ren, Xiaojia, Seth, Sahil, Yang, Lixing, Xu, Andrew W., Song, Xingzhi, Xi, Ruibin, Bristow, Christopher A., Hadjipanayis, Angela, Seidman, Jonathan, Chin, Lynda, Park, Peter J., Kucherlapati, Raju, Ling, Shiyun, Rao, Arvind, Weinstein, John N., Kim, Sang-Bae, Lu, Yiling, Mills, Gordon, Bootwalla, Moiz S., Lai, Phillip H., Triche, Timothy, Van Den Berg, David J., Baylin, Stephen B., Herman, James G., Murray, Bradley A., Askoy, B. Arman, Ciriello, Giovanni, Dresdner, Gideon, Gao, Jianjiong, Gross, Benjamin, Jacobsen, Anders, Lee, William, Ramirez, Ricardo, Sander, Chris, Senbabaoglu, Yasin, Sinha, Rileen, Sumer, S. Onur, Sun, Yichao, Thorsson, Vésteinn, Iype, Lisa, Kramer, Roger W., Kreisberg, Richard, Rovira, Hector, Tasman, Natalie, Ng, Santa Cruz Sam, Haussler, David, Stuart, Josh M., Verhaak, Roeland G.W., Leiserson, Mark D. M., Taylor, Barry S., Black, Aaron D., Carney, Julie Ann, Gastier-Foster, Julie M., Helsel, Carmen, McAllister, Cynthia, Ramirez, Nilsa C., Tabler, Teresa R., Wise, Lisa, Zmuda, Erik, Penny, Robert, Crain, Daniel, Gardner, Johanna, Lau, Kevin, Curely, Erin, Mallery, David, Morris, Scott, Paulauskis, Joseph, Shelton, Troy, Shelton, Candace, Sherman, Mark, Benz, Christopher, Lee, Jae-Hyuk, Fedosenko, Konstantin, Manikhas, Georgy, Potapova, Olga, Voronina, Olga, Belyaev, Smitry, Dolzhansky, Oleg, Rathmell, W. Kimryn, Brzezinski, Jakub, Ibbs, Matthew, Korski, Konstanty, Kycler, Witold, ŁaŸniak, Radoslaw, Leporowska, Ewa, Mackiewicz, Andrzej, Murawa, Dawid, Murawa, Pawel, Spychała, Arkadiusz, Suchorska, Wiktoria M., Tatka, Honorata, Teresiak, Marek, Abdel-Misih, Raafat, Bennett, Joseph, Brown, Jennifer, Iacocca, Mary, Rabeno, Brenda, Kwon, Sun-Young, Kemkes, Ariane, Curley, Erin, Alexopoulou, Iakovina, Engel, Jay, Bartlett, John, Albert, Monique, Park, Do-Youn, Dhir, Rajiv, Luketich, James, Landreneau, Rodney, Janjigian, Yelena Y., Cho, Eunjung, Ladanyi, Marc, Tang, Laura, McCall, Shannon J., Park, Young S., Cheong, Jae-Ho, Ajani, Jaffer, Camargo, M. Constanza, Alonso, Shelley, Ayala, Brenda, Jensen, Mark A., Pihl, Todd, Raman, Rohini, Walton, Jessica, Wan, Yunhu, Eley, Greg, Mills Shaw, Kenna R., Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean Claude, Davidsen, Tanja, Hutter, Carolyn M., Sofia, Heidi J., Burton, Robert, Chudamani, Sudha, Liu, Jia, Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Biology, Getz, Gad Asher, Sougnez, Carrie L, Jung, Joonil, Lander, Eric Steven, Lin, Pei, Meyerson, Matthew L, and Voet, Douglas

Subjects
Male, Herpesvirus 4, Human, Proteome, Biology, Adenocarcinoma, Bioinformatics, MLH1, Article, Epstein-Barr virus associated gastric carcinoma, Germline mutation, Stomach Neoplasms, medicine, Humans, Multidisciplinary, CpG Island Methylator Phenotype, Genome, Human, digestive, oral, and skin physiology, medicine.disease, digestive system diseases, Lynch syndrome, 3. Good health, Gene Expression Regulation, Neoplastic, Mutation, Cancer research, Female, DNA mismatch repair, Gastric Carcinoma with Lymphoid Stroma
Abstract

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein-Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies., National Institutes of Health (U.S.) (Grant 5U24CA143799), National Institutes of Health (U.S.) (Grant 5U24CA143835), National Institutes of Health (U.S.) (Grant 5U24CA143840), National Institutes of Health (U.S.) (Grant 5U24CA143843), National Institutes of Health (U.S.) (Grant 5U24CA143845), National Institutes of Health (U.S.) (Grant 5U24CA143848), National Institutes of Health (U.S.) (Grant 5U24CA143858), National Institutes of Health (U.S.) (Grant 5U24CA143866), National Institutes of Health (U.S.) (Grant 5U24CA143867), National Institutes of Health (U.S.) (Grant 5U24CA143882), National Institutes of Health (U.S.) (Grant 5U24CA143883), National Institutes of Health (U.S.) (Grant 5U24CA144025), National Institutes of Health (U.S.) (Grant U54HG003067), National Institutes of Health (U.S.) (Grant U54HG003079), National Institutes of Health (U.S.) (Grant U54HG003273), National Institutes of Health (U.S.) (Grant P30CA16672)

Published
2014

7. Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

Author

Zheng, Siyuan, Cherniack, Andrew D, Dewal, Ninad, Moffitt, Richard A, Danilova, Ludmila, Murray, Bradley A, Lerario, Antonio M, Else, Tobias, Knijnenburg, Theo A, Ciriello, Giovanni, Kim, Seungchan, Assie, Guillaume, Morozova, Olena, Akbani, Rehan, Shih, Juliann, Hoadley, Katherine A, Choueiri, Toni K, Waldmann, Jens, Mete, Ozgur, Robertson, A Gordon, Wu, Hsin-Ta, Raphael, Benjamin J, Shao, Lina, Meyerson, Matthew, Demeure, Michael J, Beuschlein, Felix, Gill, Anthony J, Sidhu, Stan B, Almeida, Madson Q, Fragoso, Maria CBV, Cope, Leslie M, Kebebew, Electron, Habra, Mouhammed A, Whitsett, Timothy G, Bussey, Kimberly J, Rainey, William E, Asa, Sylvia L, Bertherat, Jérôme, Fassnacht, Martin, Wheeler, David A, Cancer Genome Atlas Research Network, Hammer, Gary D, Giordano, Thomas J, and Verhaak, Roel GW

Subjects
Adult, Male, Adolescent, Outcome Assessment, Oncology and Carcinogenesis, Cancer Genome Atlas Research Network, Disease-Free Survival, Young Adult, Rare Diseases, Adrenocortical Carcinoma, 80 and over, Genetics, Humans, Genetic Predisposition to Disease, Oncology & Carcinogenesis, Child, Aged, Cancer, Neoplastic, Genome, Gene Expression Profiling, Human Genome, Neurosciences, Genomics, DNA Methylation, Middle Aged, Prognosis, Adrenal Cortex Neoplasms, Health Care, Gene Expression Regulation, Mutation, Female, Human
Abstract

We describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers.

Published
2016

8. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma

Author

Cancer Genome Atlas Research Network, Linehan, W Marston, Spellman, Paul T, Ricketts, Christopher J, Creighton, Chad J, Fei, Suzanne S, Davis, Caleb, Wheeler, David A, Murray, Bradley A, Schmidt, Laura, Vocke, Cathy D, Peto, Myron, Al Mamun, Abu Amar M, Shinbrot, Eve, Sethi, Anurag, Brooks, Samira, Rathmell, W Kimryn, Brooks, Angela N, Hoadley, Katherine A, Robertson, A Gordon, Brooks, Denise, Bowlby, Reanne, Sadeghi, Sara, Shen, Hui, Weisenberger, Daniel J, Bootwalla, Moiz, Baylin, Stephen B, Laird, Peter W, Cherniack, Andrew D, Saksena, Gordon, Haake, Scott, Li, Jun, Liang, Han, Lu, Yiling, Mills, Gordon B, Akbani, Rehan, Leiserson, Mark DM, Raphael, Benjamin J, Anur, Pavana, Bottaro, Donald, Albiges, Laurence, Barnabas, Nandita, Choueiri, Toni K, Czerniak, Bogdan, Godwin, Andrew K, Hakimi, A Ari, Ho, Thai H, Hsieh, James, Ittmann, Michael, Kim, William Y, Krishnan, Bhavani, Merino, Maria J, Mills Shaw, Kenna R, Reuter, Victor E, Reznik, Ed, Shelley, Carl S, Shuch, Brian, Signoretti, Sabina, Srinivasan, Ramaprasad, Tamboli, Pheroze, Thomas, George, Tickoo, Satish, Burnett, Kenneth, Crain, Daniel, Gardner, Johanna, Lau, Kevin, Mallery, David, Morris, Scott, Paulauskis, Joseph D, Penny, Robert J, Shelton, Candace, Shelton, W Troy, Sherman, Mark, Thompson, Eric, Yena, Peggy, Avedon, Melissa T, Bowen, Jay, Gastier-Foster, Julie M, Gerken, Mark, Leraas, Kristen M, Lichtenberg, Tara M, Ramirez, Nilsa C, Santos, Tracie, Wise, Lisa, Zmuda, Erik, Demchok, John A, Felau, Ina, Hutter, Carolyn M, Sheth, Margi, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Ayala, Brenda, Baboud, Julien, Chudamani, Sudha, Liu, Jia, and Lolla, Laxmi

Subjects
Kidney Disease, NF-E2-Related Factor 2, Papillary, Messenger, Cancer Genome Atlas Research Network, Medical and Health Sciences, Rare Diseases, General & Internal Medicine, Genetics, Humans, Cancer, Carcinoma, DNA Methylation, Proto-Oncogene Proteins c-met, Kidney Neoplasms, MicroRNAs, Phenotype, Good Health and Well Being, Mutation, RNA, Neoplasm, CpG Islands, Digestive Diseases, Sequence Analysis, Signal Transduction, Biotechnology
Abstract

BackgroundPapillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist.MethodsWe performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis.ResultsType 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH).ConclusionsType 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

Published
2016

9. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma

Author

Tirapelli, Daniel Pretti da Cunha, Cooper, Lee, Ling, Shiyun, Verhaak, Roel G.W., Zhang, Hailei, Wrensch, Margaret, Radenbaugh, Amie, Yung, W.K. Alfred, Grifford, Mia, Mikkelsen, Tom, Meyerson, Matthew, Huse, Jason, TCGA Research Network, Zoppoli, Pietro, Lau, Ching C., Barnholtz-Sloan, Jill S., Laird, Peter W., Akbani, Rehan, Anjum, Samreen, Noushmehr, Houtan, Zheng, Siyuan, Iavarone, Antonio, Malta, Tathiane, Rao, Ganesh, Rao, Aravind, Sabedot, Thais, Newton, Yulia, Carolotti, Jr., Carlos Gilberto, Rao, Arjun A., Pagnotta, Stefano, Gutmann, David, Manyam, Ganiraju, Poisson, Laila, Aldape, Kenneth, Rabadan, Raul, Murray, Bradley, Salama, Sofie, Barthel, Floris P., Haussler, David, Hess, Kenneth, Ceccarelli, Michele, Lehrman, Norman L., Cherniack, Andrew D., Morozova, Olena, Beroukhim, Rameen, Brat, Daniel J., and Wang, Jiguang

Subjects
Adult, X-linked Nuclear Protein, TCGA Research Network, Medical and Health Sciences, Promoter Regions, Rare Diseases, Genetic, Genetics, Humans, Cluster Analysis, Telomerase, Cell Proliferation, Cancer, Brain Neoplasms, Human Genome, DNA Helicases, Neurosciences, Nuclear Proteins, Glioma, Telomere, DNA Methylation, Middle Aged, Biological Sciences, Isocitrate Dehydrogenase, Brain Disorders, Brain Cancer, Orphan Drug, Mutation, Transcriptome, Signal Transduction, Epigenesis, Biotechnology, Developmental Biology
Abstract

Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes.

Published
2016

10. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas

Author

Cancer Genome Atlas Research Network, Brat, Daniel J, Verhaak, Roel GW, Aldape, Kenneth D, Yung, WK Alfred, Salama, Sofie R, Cooper, Lee AD, Rheinbay, Esther, Miller, C Ryan, Vitucci, Mark, Morozova, Olena, Robertson, A Gordon, Noushmehr, Houtan, Laird, Peter W, Cherniack, Andrew D, Akbani, Rehan, Huse, Jason T, Ciriello, Giovanni, Poisson, Laila M, Barnholtz-Sloan, Jill S, Berger, Mitchel S, Brennan, Cameron, Colen, Rivka R, Colman, Howard, Flanders, Adam E, Giannini, Caterina, Grifford, Mia, Iavarone, Antonio, Jain, Rajan, Joseph, Isaac, Kim, Jaegil, Kasaian, Katayoon, Mikkelsen, Tom, Murray, Bradley A, O'Neill, Brian Patrick, Pachter, Lior, Parsons, Donald W, Sougnez, Carrie, Sulman, Erik P, Vandenberg, Scott R, Van Meir, Erwin G, von Deimling, Andreas, Zhang, Hailei, Crain, Daniel, Lau, Kevin, Mallery, David, Morris, Scott, Paulauskis, Joseph, Penny, Robert, Shelton, Troy, Sherman, Mark, Yena, Peggy, Black, Aaron, Bowen, Jay, Dicostanzo, Katie, Gastier-Foster, Julie, Leraas, Kristen M, Lichtenberg, Tara M, Pierson, Christopher R, Ramirez, Nilsa C, Taylor, Cynthia, Weaver, Stephanie, Wise, Lisa, Zmuda, Erik, Davidsen, Tanja, Demchok, John A, Eley, Greg, Ferguson, Martin L, Hutter, Carolyn M, Mills Shaw, Kenna R, Ozenberger, Bradley A, Sheth, Margi, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean Claude, Ayala, Brenda, Baboud, Julien, Chudamani, Sudha, Jensen, Mark A, Liu, Jia, Pihl, Todd, Raman, Rohini, Wan, Yunhu, Wu, Ye, Ally, Adrian, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Baylin, Stephen B, Beroukhim, Rameen, Bootwalla, Moiz S, Bowlby, Reanne, Bristow, Christopher A, Brooks, Denise, Butterfield, Yaron, Carlsen, Rebecca, Carter, Scott, and Chin, Lynda

Subjects
p53, Adult, Male, Adolescent, Cancer Genome Atlas Research Network, Kaplan-Meier Estimate, Medical and Health Sciences, Chromosomes, Rare Diseases, General & Internal Medicine, Genetics, Humans, Cluster Analysis, Proportional Hazards Models, Aged, Cancer, Pair 19, Human Genome, Glioma, DNA, Middle Aged, Brain Disorders, Brain Cancer, Genes, Mutation, Pair 1, Neoplasm, Female, Neoplasm Grading, Glioblastoma, Sequence Analysis, Human, Signal Transduction
Abstract

BackgroundDiffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas.MethodsWe performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes.ResultsUnsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma.ConclusionsThe integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most lower-grade gliomas without an IDH mutation were molecularly and clinically similar to glioblastoma. (Funded by the National Institutes of Health.).

Published
2015

11. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer

Author

Gehlenborg, Nils, Mills, Gordon B., Ramirez, Nilsa C., Mungall, Andrew J., Zhang, Hailei, Schultz, Nikolaus, Ding, Li, Wang, Zhining, Sofia, Heidi J., Felau, Ina, Murray, Bradley A., Wiznerowicz, MacIej, Brooks, Denise, Yang, Liming, Shriver, Craig, Chin, Lynda, Jefferys, Stuart R., Perou, Charles M., Gibson, William J., Holbrook, Andrea, Jones, Steven J.M., Shi, Yan, Gatza, Michael L., Tarnuzzer, Roy, Roach, Jeffrey, Gabriel, Stacey B., Shaw, Kenna R.Mills, Beroukhim, Rameen, Robertson, A. Gordon, Hoyle, Alan P., Lolla, Laxmi, Holt, Robert A., Olopade, Olufunmilayo, Wu, Junyuan, Zack, Travis I., Davidsen, Tanja, Naresh, Rashi, Kim, Jaegil, Liu, Wenbin, Gastier-Foster, Julie M., Liu, Jia, Pastore, Alessandro, Wilson, Richard, Frazer, Scott, Benz, Christopher, Huang, Mei, Schein, Jacqueline E., Kandoth, Cyriac, Rhie, Suhn K., Soloway, Matthew G., Hwang, E. Shelley, Boice, Lori, Cho, Juok, Meyerson, Matthew, Benz, Stephen, Saksena, Gordon, Fieldhouse, Robert, Hu, Hai, Leraas, Kristen M., Laird, Peter W., King, Tari A., Getz, Gad, Ju, Zhenlin, Johnson, Nicole B., McAllister, Cynthia, Pihl, Todd, Marks, Jeffrey, Sun, Charlie, Wise, Lisa, Ling, Shiyun, Lichtenberg, Tara M., Barr, Thomas, Balasundaram, Miruna, Gerken, Mark, Weinstein, John N., Lester, Susan C., Weisenberger, Daniel J., Tse, Gary M.K., Zhang, Jiashan, Marra, Marco A., Shen, Hui, Sander, Chris, Chudamani, Sudha, Zmuda, Erik, Parker, Joel S., Collins, Laura C., Tiezzi, Daniel G., Hutter, Carolyn M., Zenklusen, Jean C., Sougnez, Carrie, Lawrence, Michael S., Lu, Yiling, Bowlby, Reanne, Robertson, Gordon, Moore, Richard A., Simons, Janae V., Bootwalla, Moiz S., Meng, Shaowu, Cherniack, Andrew D., Shih, Juliann, Hoadley, Katherine A., Berrios, Mario, Auman, J. Todd, Akbani, Rehan, Beck, Andrew H., McLellan, Michael, Demchok, John A., Maglinte, Dennis T., Schumacher, Steven E., Lai, Phillip H., Bodenheimer, Tom, Allison, Kimberly H., Bowen, Jay, Yau, Christina, Gao, Jian Jiong, Ferguson, Martin L., Mose, Lisle E., Sheth, Margi, Jensen, Kristin, Mardis, Elaine, Van Den Berg, David J., Voet, Doug, Heiman, David I., Hayes, D. Neil, Oesterreich, Steffi, Rathmell, W. Kimryn, Wilkerson, Matthew D., Lin, Pei, Ma, Yussanne, Hayat, Sikander, Balu, Saianand, Noble, Michael S., Shelley, Carl Simon, Chen, Yunn Yi, Factor, Rachel E., Wu, Ye, Wan, Yunhu, Ciriello, Giovanni, and Dennison, Jennifer B.

Subjects
body regions, skin and connective tissue diseases
Abstract

Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3 and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized Luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options.

Published
2015
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12. Swapping information in high places — Sanitation decisions in Ethiopia

Author

Sarah Murray Bradley

Subjects
Sanitation, Environmental protection, Open defecation, Business, Environmental planning, Water Science and Technology, Local community
Abstract

A basic sanitation workshop in Ethiopia worked with the local community and helped local public heath officials to kickstart their own sanitation campaign.

Published
1994
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13. Integrated genomic and molecular characterization of cervical cance

Author

Burk, Robert D., Chen, Zigui, Saller, Charles, Tarvin, Katherine, Carvalho, Andre L., Scapulatempo-Neto, Cristovam, Silveira, Henrique C., Fregnani, Jose 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., 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., Byers, Lauren Averett, 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, Carlotti, Carlos Gilberto, Tirapelli, Daniela Pretti Da Cunha, Weisenberger, Daniel J., David J Van Den Berg, Maglinte, Dennis T., Bootwalla, Moiz S., Lai, Phillip H., Triche, Timothy, Swisher, Elizabeth M., Agnew, Kathy J., Shelley, Carl Simon, Laird, Peter W., Schwarz, Julie, Grigsby, Perry, Mutch, David, and Canc Genome Atlas Res Network

14. Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

Author

Santibanez, Jireh, Robertson, A. Gordon, Meng, Shaowu, Pihl, Todd, Auman, J. Todd, Wilkerson, Matthew D., Hoadley, Katherine A., Bussey, Kimberly J., Wu, Hsin-Ta, Crawford, Catherine, Sibony, Mathilde, Cope, Leslie M., Arachchi, Harindra, Sander, Chris, Wang, Zhining, Gill, Anthony J., Bodenheimer, Tom, Shinbrot, Eve, Mayo, Michael, Hu, Jianhong, Liu, Jia, Choueiri, Toni K., Mills, Gordon B., Davidsen, Tanja, Raphael, Benjamin J., Balu, Saianand, Ciriello, Giovanni, Jones, Corbin D., Guin, Ranabir, Hammer, Gary D., Lerario, Antonio M., Hoyle, Alan P., Weisenberger, Daniel J., Giordano, Thomas J., Radenbaugh, Amie, Cho, Juok, Ling, Shiyun, Sofia, Heidi J., Zhu, Jingchun, Wu, Junyuan, Khan, Ziad, Amble, Linda, Naresh, Rashi, Dousset, Bertrand, Shao, Lina, Shih, Juliann, Waldmann, Jens, Coppens, Sara, Lee, Darlene, Demchok, John A., Doddapaneni, Harsha, Danilova, Ludmila, Wang, Wenyi, Mose, Lisle E., Kim, Hoon, Beroukhim, Rameen, Morgan, Margaret, Wan, Yunhu, Hutter, Carolyn M., Kovar, Christine, Latronico, Ana Claudia, Rao, Arjun, Marra, Marco A., Knijnenburg, Theo A., Almeida, Madson Q., Ju, Zhenlin, Sougnez, Carrie, Kroiss, Matthias, Shi, Yan, Wu, Ye, Shmulevich, Ilya, Gaudioso, Carmelo, Akbani, Rehan, Mungall, Karen, Felau, Ina, Schein, Jacqueline E., Gibbs, Richard, Morozova, Olena, Moffitt, Richard A., Weinstein, John N., Fragoso, Maria C.B.V., Verhaak, Roel G.W., Dewal, Ninad, Soloway, Matthew G., Kalra, Divya, Lawrence, Michael S., Defreitas, Timothy, Ronchi, Cristina, Kasaian, Katayoon, Park, Peter J., Demeure, Michael J., Hayes, D. Neil, Herman, James G., Parker, Joel S., Morton, Donna, Reincke, Martin, Han, Yi, Lee, Sandy, Sanborn, Zack, Wheeler, David A., Xi, Liu, Lim, Lynette, Soon, Patsy, Leraas, Kristen M., Zmuda, Erik, Buhay, Christian, Benz, Christopher, Bowlby, Reanne, Liu, Wenbin, Fan, Yu, Cherniack, Andrew D., Bootwalla, Moiz S., Hawes, Alicia, Mendonca, Berenice B., Sidhu, Stan B., Noble, Michael S., Alonso, Shelley, Van Den Berg, David J., Raman, Rohini, Bshara, Wiam, Murray, Bradley A., Zenklusen, Jean C., Laird, Peter W., Beuschlein, Felix, Carter, Scott L., Tarnuzzer, Roy, Schumacher, Steven E., Gerken, Mark, Saksena, Gordon, Kim, Seungchan, Else, Tobias, Allolio, Bruno, Sun, Qiang, Mungall, Andrew J., Jefferys, Stuart R., Zheng, Siyuan, Frazer, Scott, Gao, Jianjiong, Morrison, Carl, Lin, Pei, Butterfield, Yaron S.N., Lai, Phillip H., Groussin, Lionel, Raymond, Victoria M., Ma, Yussanne, Bertherat, Jérôme, Meier, Sam, Gabriel, Stacey B., Mieczkowski, Piotr A., Meyerson, Matthew, Lu, Yiling, Zhang, Jiashan, Whitsett, Timothy G., Yeh, Jen Jen, Brooks, Denise, Dhalla, Noreen, Perou, Charles M., Roach, Jeffrey, Libé, Rossella, Rainey, William E., Ladanyi, Marc, Thiessen, Nina, Lolla, Laxmi, Wang, Qianghu, Holt, Robert A., Tam, Angela, Zhang, Wei, Watanabe, Aprill, Moore, Richard A., Reynolds, Sheila, Baylin, Stephen, Chudamani, Sudha, Simons, Janae V., Zhang, Hailei, Asa, Sylvia L., Lichtenberg, Tara M., Quinkler, Marcus, Ramirez, Nilsa C., Hale, Walker, Voet, Doug, Bowen, Jay, Chin, Lynda, Bartsch, Detlef K., Sadeghi, Sara, Getz, Gad, Covington, Kyle, Wise, Lisa, Veluvolu, Umadevi, Li, Haiyan I., Sipahimalani, Payal, Sheth, Margi, Fassnacht, Martin, Carlsen, Rebecca, Gastier-Foster, Julie M., Haussler, David, Baboud, Julien, Tan, Donghui, Yoshihara, Kosuke, Habra, Mouhammed A., Kucherlapati, Raju, Muzny, Donna, Kim, Jaegil, Sbiera, Silviu, Downs, Brittany, Drummond, Jennifer, Yang, Liming, Schultz, Nikolaus, Deutschbein, Timo, Ally, Adrian, Dinh, Huyen, Balasundaram, Miruna, Sircar, Kanishka, Kakkar, Nipun, Helsel, Carmen, Lewis, Lora, Kebebew, Electron, Jones, Steven J.M., Dahdouli, Mahmoud, Heiman, David I., Robinson, Bruce, LoBello, Janine, Shaw, Kenna R. Mills, Mete, Ozgur, Vinco, Michelle, Assie, Guillaume, and Bellair, Michelle

Subjects
3. Good health
Abstract

SummaryWe describe a comprehensive genomic characterization of adrenocortical carcinoma (ACC). Using this dataset, we expand the catalogue of known ACC driver genes to include PRKAR1A, RPL22, TERF2, CCNE1, and NF1. Genome wide DNA copy-number analysis revealed frequent occurrence of massive DNA loss followed by whole-genome doubling (WGD), which was associated with aggressive clinical course, suggesting WGD is a hallmark of disease progression. Corroborating this hypothesis were increased TERT expression, decreased telomere length, and activation of cell-cycle programs. Integrated subtype analysis identified three ACC subtypes with distinct clinical outcome and molecular alterations which could be captured by a 68-CpG probe DNA-methylation signature, proposing a strategy for clinical stratification of patients based on molecular markers.

15. Integrated genomic characterization of oesophageal carcinoma

Author

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

Subjects
3. Good health
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.

16. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

Author

Kasaian, Katayoon, Veluvolu, Umadevi, Berrios, Mario, Kleiner, David E., Tan, Donghui, Gardner, Johanna, Cherniack, Andrew D., Bowlby, Reanne, Shinbrot, Eve, Parker, Joel S., Deshpande, Vikram, Mungall, Andrew J., O’Brien, Daniel R., Farshidfar, Farshad, Laird, Peter W., Yang, Ju Dong, Jones, Steven J.M., Roach, Jeffrey, Chandan, Vishal C., Foo, Wai Chin, Weinstein, John N., Liu, Wenbin, Ojesina, Akinyemi I., Hinoue, Toshinori, Perou, Amy H., Wu, Chia-Chin, Leraas, Kristen M., Auman, J. Todd, Arora, Arshi, Lai, Phillip H., Skelly, Tara, Zenklusen, Jean C., Holbrook, Andrea, Giama, Nasra H., Wang, Zhining, Mills, Gordon B., Gibbs, Richard A., Zmuda, Erik, Reznik, Ed, Demchok, John A., Xi, Liu, Wu, Ye, Tam, Angela, Hegde, Apurva M., Chuah, Eric, Stoppler, Hubert, Covington, Kyle R., Bowen, Jay, Carpino, Guido, Robertson, A. Gordon, Zhu, Andrew X., Hayes, D. Neil, Pihl, Todd, Cordes, Matthew G., Naresh, Rashi, Cardinale, Vincenzo, Huang, Mei, Rathmell, W. Kimryn, Gingras, Marie-Claude, Mayo, Michael, Zhang, Jiashan (Julia), Shen, Ronglai, Bathe, Oliver F., Wheeler, David A., Ma, Yussanne, Patel, Tushar C., Murray, Bradley A., Fulton, Lucinda A., Matsushita, Marcus M., Chaiteerakij, Roongruedee, Crain, Daniel, Wilson, Richard K., Shelton, Candace, Schumacher, Steven E., Moore, Richard A., Gaudio, Eugenio, Paulauskis, Joseph, De Rose, Agostino Maria, Carvalho, Andre L., Roberts, Lewis R., Lawrence, Michael S., Wong, Tina, Bardeesy, Nabeel, Mallery, David, Chin, Lynda, Soloway, Matthew G., Simons, Janae V., Bodenheimer, Tom, Jones, Corbin D., Morris, Scott, Genovese, Giannicola, Kim, Jaegil, Andersen, Jesper B., Appelbaum, Elizabeth L., Shroff, Rachna, Thiessen, Nina, Alvaro, Domenico, Brooks, Denise, Sun, Qiang, Schein, Jacqueline E., Sofia, Heidi J., Evason, Kimberley, Weisenberger, Daniel J., Allotey, Loretta K., Bootwalla, Moiz S., Fulton, Robert S., Marra, Marco A., Beroukhim, Rameen, Sheth, Margi, Pedamallu, Chandra Sekhar, Lu, Yiling, Boice, Lori, Hoadley, Katherine A., Noble, Michael S., Grazi, Gian Luca, Kocher, Jean-Pierre A., Ally, Adrian, Kwong, Lawrence N., Meng, Shaowu, Moser, Catherine D., Gibb, Ewan A., Hutter, Carolyn M., Zheng, Siyuan, Shi, Yan, McLellan, Michael D., Giuliante, Felice, Van Den Berg, David J., Ramirez, Nilsa C., Thorne, Leigh B., Sander, Chris, McRee, Autumn J., Bragazzi, Maria Consiglia, Getz, Gad, Mose, Lisle E., Zhang, Hailei, Ding, Li, Shih, Juliann, Tarnuzzer, Roy, Rhie, Suhn K., Meier, Sam, Baylin, Stephen B., Cho, Juok, Miller, Christopher A., Felau, Ina, Mieczkowski, Piotr A., Shelton, Troy, Cibulskis, Carrie, Schmidt, Heather K., Borad, Mitesh J., Balu, Saianand, Jefferys, Stuart R., Ferguson, Martin L., Saksena, Gordon, Mardis, Elaine R., Sadeghi, Sara, Hoyle, Alan P., Frazer, Scott, Stransky, Nicolas, Carlsen, Rebecca, Roszik, Jason, Wan, Yunhu, Defreitas, Timothy, Mounajjed, Taofic, Fronick, Catrina C., Balasundaram, Miruna, Gabriel, Stacey B., Penny, Robert, Yang, Liming, Newton, Yulia, Perou, Charles M., Lin, Pei, Holt, Robert A., Chudamani, Sudha, Radenbaugh, Amie J., Mungall, Karen, Stuart, Josh, Kelley, Robin K., Curley, Erin, Lolla, Laxmi, Verhaak, Roel G.W., Liu, Jia, Dhalla, Noreen, Heiman, David I., Gehlenborg, Nils, Choe, Gina, Wise, Lisa, Gerken, Mark, Franchitto, Antonio, Gastier-Foster, Julie M., Lichtenberg, Tara M., Akbani, Rehan, Hess, Julian M., Torbenson, Michael S., Meyerson, Matthew, Voet, Doug, and Sipahimalani, Payal

Subjects
3. Good health
Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

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