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Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma.

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.

SUBMITTER: Zheng S 

PROVIDER: S-EPMC4864952 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma.

Zheng Siyuan S   Cherniack Andrew D AD   Dewal Ninad N   Moffitt Richard A RA   Danilova Ludmila L   Murray Bradley A BA   Lerario Antonio M AM   Else Tobias T   Knijnenburg Theo A TA   Ciriello Giovanni G   Kim Seungchan S   Assie Guillaume G   Morozova Olena O   Akbani Rehan R   Shih Juliann J   Hoadley Katherine A KA   Choueiri Toni K TK   Waldmann Jens J   Mete Ozgur O   Robertson A Gordon AG   Wu Hsin-Ta HT   Raphael Benjamin J BJ   Shao Lina L   Meyerson Matthew M   Demeure Michael J MJ   Beuschlein Felix F   Gill Anthony J AJ   Sidhu Stan B SB   Almeida Madson Q MQ   Fragoso Maria C B V MCBV   Cope Leslie M LM   Kebebew Electron E   Habra Mouhammed A MA   Whitsett Timothy G TG   Bussey Kimberly J KJ   Rainey William E WE   Asa Sylvia L SL   Bertherat Jérôme J   Fassnacht Martin M   Wheeler David A DA   Hammer Gary D GD   Giordano Thomas J TJ   Verhaak Roel G W RGW  

Cancer cell 20160501 5

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 expressi  ...[more]

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