Comprehensive pan-genomic characterization of adrenocortical carcinoma

The Cancer Genome Atlas Research Network

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    232 Scopus citations

    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, 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.

    Original languageEnglish (US)
    Pages (from-to)723-736
    Number of pages14
    JournalCancer Cell
    Volume29
    Issue number5
    DOIs
    StatePublished - May 9 2016

    ASJC Scopus subject areas

    • Oncology
    • Cell Biology
    • Cancer Research

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