TY - JOUR
T1 - Comprehensive pan-genomic characterization of adrenocortical carcinoma
AU - The Cancer Genome Atlas Research Network
AU - Zheng, Siyuan
AU - Cherniack, Andrew D.
AU - Dewal, Ninad
AU - Moffitt, Richard A.
AU - Danilova, Ludmila
AU - Murray, Bradley A.
AU - Lerario, Antonio M.
AU - Else, Tobias
AU - Knijnenburg, Theo A.
AU - Ciriello, Giovanni
AU - Kim, Seungchan
AU - Assie, Guillaume
AU - Morozova, Olena
AU - Akbani, Rehan
AU - Shih, Juliann
AU - Hoadley, Katherine A.
AU - Choueiri, Toni K.
AU - Waldmann, Jens
AU - Mete, Ozgur
AU - Robertson, A. Gordon
AU - Wu, Hsin Ta
AU - Raphael, Benjamin J.
AU - Shao, Lina
AU - Meyerson, Matthew
AU - Demeure, Michael J.
AU - Beuschlein, Felix
AU - Gill, Anthony J.
AU - Sidhu, Stan B.
AU - Almeida, Madson Q.
AU - Fragoso, Maria C.B.V.
AU - Cope, Leslie M.
AU - Kebebew, Electron
AU - Habra, Mouhammed A.
AU - Whitsett, Timothy G.
AU - Bussey, Kimberly J.
AU - Rainey, William E.
AU - Asa, Sylvia L.
AU - Bertherat, Jérôme
AU - Fassnacht, Martin
AU - Wheeler, David A.
AU - Hammer, Gary D.
AU - Giordano, Thomas J.
AU - Verhaak, Roel G.W.
AU - Benz, Christopher
AU - Ally, Adrian
AU - Balasundaram, Miruna
AU - Bowlby, Reanne
AU - Brooks, Denise
AU - Butterfield, Yaron S.N.
AU - Baylin, Stephen
N1 - Funding Information:
We are grateful to all the patients and families who contributed to this study, to Ina Felau, Margi Sheth, and Jiashan (Julia) Zhang for project management. Supported by the following grants from the United States NIH : 5U24CA143799 , 5U24CA143835 , 5U24CA143840 , 5U24CA143843 , 5U24CA143845 , 5U24CA143848 , 5U24CA143858 , 5U24CA143866 , 5U24CA143867 , 5U24CA143882 , 5U24CA143883 , 5U24CA144025 , U54HG003067 , U54HG003079 , and U54HG003273 , P30CA16672 . G.D.H. has equity interest in, is a consultant for, and scientific advisory board director of Millendo Therapeutics. R.B. is a consultant for and received grant funding from Novartis . J.S., B.A.M., A.D.C., and M.M. received grant support from Bayer . S.L.A. is a member of the Medical Advisory Board of Leica Aperio. D.J.W. is a consultant for Zymo Research Corporation.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/5/9
Y1 - 2016/5/9
N2 - 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, suggestingWGDis 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.
AB - 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, suggestingWGDis 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.
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U2 - 10.1016/j.ccell.2016.04.002
DO - 10.1016/j.ccell.2016.04.002
M3 - Article
C2 - 27165744
AN - SCOPUS:84975223445
SN - 1535-6108
VL - 29
SP - 723
EP - 736
JO - Cancer cell
JF - Cancer cell
IS - 5
ER -