| Literature DB >> 27165744 |
Siyuan Zheng1, Andrew D Cherniack2, Ninad Dewal3, Richard A Moffitt4, Ludmila Danilova5, Bradley A Murray2, Antonio M Lerario6, Tobias Else7, Theo A Knijnenburg8, Giovanni Ciriello9, Seungchan Kim10, Guillaume Assie11, Olena Morozova12, Rehan Akbani1, Juliann Shih2, Katherine A Hoadley4, Toni K Choueiri13, Jens Waldmann14, Ozgur Mete15, A Gordon Robertson16, Hsin-Ta Wu17, Benjamin J Raphael17, Lina Shao18, Matthew Meyerson19, Michael J Demeure10, Felix Beuschlein20, Anthony J Gill21, Stan B Sidhu22, Madson Q Almeida23, Maria C B V Fragoso23, Leslie M Cope5, Electron Kebebew24, Mouhammed A Habra1, Timothy G Whitsett10, Kimberly J Bussey25, William E Rainey7, Sylvia L Asa15, Jérôme Bertherat11, Martin Fassnacht26, David A Wheeler3, Gary D Hammer7, Thomas J Giordano27, Roel G W Verhaak28.
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.Entities:
Mesh：
Year: 2016 PMID： 27165744 PMCID： PMC4864952 DOI： 10.1016/j.ccell.2016.04.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743