Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma.

TitleComprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma.
Publication TypeJournal Article
Year of Publication2016
AuthorsZheng, S, Cherniack, AD, Dewal, N, Moffitt, RA, Danilova, L, Murray, BA, Lerario, AM, Else, T, Knijnenburg, TA, Ciriello, G, Kim, S, Assie, G, Morozova, O, Akbani, R, Shih, J, Hoadley, KA, Choueiri, TK, Waldmann, J, Mete, O, A Robertson, G, Wu, H-T, Raphael, BJ, Shao, L, Meyerson, M, Demeure, MJ, Beuschlein, F, Gill, AJ, Sidhu, SB, Almeida, MQ, Fragoso, MCBV, Cope, LM, Kebebew, E, Habra, MA, Whitsett, TG, Bussey, KJ, Rainey, WE, Asa, SL, Bertherat, J, Fassnacht, M, Wheeler, DA, Hammer, GD, Giordano, TJ, Verhaak, RGW
Corporate AuthorsCancer Genome Atlas Research Network
JournalCancer Cell
Volume29
Issue5
Pagination723-736
Date Published2016 May 09
ISSN1878-3686
KeywordsAdolescent, Adrenal Cortex Neoplasms, Adrenocortical Carcinoma, Adult, Aged, Aged, 80 and over, Child, Disease-Free Survival, DNA Methylation, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genetic Predisposition to Disease, Genome, Human, Genomics, Humans, Male, Middle Aged, Mutation, Outcome Assessment, Health Care, Prognosis, Young Adult
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.
DOI10.1016/j.ccell.2016.04.002
Alternate JournalCancer Cell
PubMed ID27165744
PubMed Central IDPMC4864952
Grant ListP30 CA016672 / CA / NCI NIH HHS / United States
U24 CA143882 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
U24 CA143835 / CA / NCI NIH HHS / United States
P30 CA046592 / CA / NCI NIH HHS / United States
U24 CA143866 / CA / NCI NIH HHS / United States
U24 CA143845 / CA / NCI NIH HHS / United States
U24 CA143799 / CA / NCI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
U24 CA144025 / CA / NCI NIH HHS / United States
U24 CA180951 / CA / NCI NIH HHS / United States
U24 CA143840 / CA / NCI NIH HHS / United States
U24 CA143843 / CA / NCI NIH HHS / United States
U24 CA210974 / CA / NCI NIH HHS / United States
U24 CA143858 / CA / NCI NIH HHS / United States
U24 CA143848 / CA / NCI NIH HHS / United States
U54 HG003079 / HG / NHGRI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
U24 CA199461 / CA / NCI NIH HHS / United States

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