1. Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma
- Author
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Siyuan Zheng, Andrew D. Cherniack, Ninad Dewal, Richard A. Moffitt, Ludmila Danilova, Bradley A. Murray, Antonio M. Lerario, Tobias Else, Theo A. Knijnenburg, Giovanni Ciriello, Seungchan Kim, Guillaume Assie, Olena Morozova, Rehan Akbani, Juliann Shih, Katherine A. Hoadley, Toni K. Choueiri, Jens Waldmann, Ozgur Mete, A. Gordon Robertson, Hsin-Ta Wu, Benjamin J. Raphael, Lina Shao, Matthew Meyerson, Michael J. Demeure, Felix Beuschlein, Anthony J. Gill, Stan B. Sidhu, Madson Q. Almeida, Maria C.B.V. Fragoso, Leslie M. Cope, Electron Kebebew, Mouhammed A. Habra, Timothy G. Whitsett, Kimberly J. Bussey, William E. Rainey, Sylvia L. Asa, Jérôme Bertherat, Martin Fassnacht, David A. Wheeler, Gary D. Hammer, Thomas J. Giordano, Roel G.W. Verhaak, Guillaume Assié, Hsin-Tu Wu, Madson Almeida, Maria Candida Barisson Fragoso, Mouhammed Amir Habra, Christopher Benz, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Yaron S.N. Butterfield, Rebecca Carlsen, Noreen Dhalla, Ranabir Guin, Robert A. Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Haiyan I. Li, Lynette Lim, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Peter J. Park, Matthias Kroiss, Jianjiong Gao, Chris Sander, Nikolaus Schultz, Corbin D. Jones, Raju Kucherlapati, Piotr A. Mieczkowski, Joel S. Parker, Charles M. Perou, Donghui Tan, Umadevi Veluvolu, Matthew D. Wilkerson, D. Neil Hayes, Marc Ladanyi, Marcus Quinkler, J. Todd Auman, Ana Claudia Latronico, Berenice B. Mendonca, Mathilde Sibony, Zack Sanborn, Michelle Bellair, Christian Buhay, Kyle Covington, Mahmoud Dahdouli, Huyen Dinh, Harsha Doddapaneni, Brittany Downs, Jennifer Drummond, Richard Gibbs, Walker Hale, Yi Han, Alicia Hawes, Jianhong Hu, Nipun Kakkar, Divya Kalra, Ziad Khan, Christine Kovar, Sandy Lee, Lora Lewis, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Liu Xi, Bertrand Dousset, Lionel Groussin, Rossella Libé, Lynda Chin, Sheila Reynolds, Ilya Shmulevich, Sudha Chudamani, Jia Liu, Laxmi Lolla, Ye Wu, Jen Jen Yeh, Saianand Balu, Tom Bodenheimer, Alan P. Hoyle, Stuart R. Jefferys, Shaowu Meng, Lisle E. Mose, Yan Shi, Janae V. Simons, Matthew G. Soloway, Junyuan Wu, Wei Zhang, Kenna R. Mills Shaw, John A. Demchok, Ina Felau, Margi Sheth, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Tanja Davidsen, Catherine Crawford, Carolyn M. Hutter, Heidi J. Sofia, Jeffrey Roach, Wiam Bshara, Carmelo Gaudioso, Carl Morrison, Patsy Soon, Shelley Alonso, Julien Baboud, Todd Pihl, Rohini Raman, Qiang Sun, Yunhu Wan, Rashi Naresh, Harindra Arachchi, Rameen Beroukhim, Scott L. Carter, Juok Cho, Scott Frazer, Stacey B. Gabriel, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Michael S. Noble, Gordon Saksena, Steven E. Schumacher, Carrie Sougnez, Doug Voet, Hailei Zhang, Jay Bowen, Sara Coppens, Julie M. Gastier-Foster, Mark Gerken, Carmen Helsel, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Stephen Baylin, James G. Herman, Janine LoBello, Aprill Watanabe, David Haussler, Amie Radenbaugh, Arjun Rao, Jingchun Zhu, Detlef K. Bartsch, Silviu Sbiera, Bruno Allolio, Timo Deutschbein, Cristina Ronchi, Victoria M. Raymond, Michelle Vinco, Linda Amble, Moiz S. Bootwalla, Phillip H. Lai, David J. Van Den Berg, Daniel J. Weisenberger, Bruce Robinson, Zhenlin Ju, Hoon Kim, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kanishka Sircar, Qianghu Wang, Kosuke Yoshihara, Peter W. Laird, Yu Fan, Wenyi Wang, Eve Shinbrot, Martin Reincke, John N. Weinstein, Sam Meier, and Timothy Defreitas
- Subjects
Adult ,Male ,0301 basic medicine ,Cancer Research ,Adolescent ,Genomics ,Biology ,Genome ,TERF2 ,Article ,Disease-Free Survival ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Outcome Assessment, Health Care ,Adrenocortical Carcinoma ,medicine ,Humans ,Adrenocortical carcinoma ,Genetic Predisposition to Disease ,Child ,Aged ,Aged, 80 and over ,Genetics ,Genome, Human ,business.industry ,Gene Expression Profiling ,Cell Biology ,DNA Methylation ,Middle Aged ,Prognosis ,medicine.disease ,Adrenal Cortex Neoplasms ,Human genetics ,3. Good health ,Gene Expression Regulation, Neoplastic ,Gene expression profiling ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Mutation ,Cancer cell ,DNA methylation ,Cancer research ,Female ,Human genome ,business - 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
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