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Home > Publications > Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma, 2016

Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma

Cancer Cell, Volume 29, Issue 5, pages 723–736

DOI: http://dx.doi.org/10.1016/j.ccell.2016.04.002

Abstract

Adrenocortical carcinoma (ACC) is a rare neoplasm with a heterogeneous outcome and limited treatment options. Here we describe the genomic, transcriptomic, epigenomic and proteomic profiling of 91 ACCs as a part of The Cancer Genome Atlas (TCGA). We identified potential driving alterations including amplifications (TERT, TERF2 and CDK4), deletions (ZNRF3, CDKN2A and RB1) and point mutations in genes previously not known to participate in adrenal disease (RPL22), as well as in genes known to initiate familial syndromes that include adrenocortical neoplasms (TP53, CTNNB1, PRKAR1A, MEN1). We observed a wide variability in ploidy in absolute copy number and genotypic analysis, which implies a sequential development from hypodiploidy to polyploidy via whole genome doubling in a subset of ACCs. Integrated analyses confirmed and expanded the role of mutations of the RB, Wnt/-catenin and PKA signaling pathways. Unsupervised clustering of multidimensional data revealed three classes of ACC with biological and clinical significance. Using genomic data of other tumour types, we performed pan-cancer analyses of ACC, which allowed us to place ACC in a broader context of cancer genomic profiles. Our results present a comprehensive genomic landscape and a refined molecular classification of ACC, improving our understanding of its pathogenesis that will ultimately improve the care of patients.

Supplementary Data Files

Associated Data Files

These data represent a data freeze from Aug 15, 2014. Please note that more recent data are available via the TCGA Data Portal.

The data are supported by different organizations. All data marked by [DCC] are DCC-validated archives. All data marked by [Supplementary] were created by the manuscript authors and you should contact the corresponding author for support.

Full Disease Sample List:

Exome Sequence BAM File References

Clinical - XML files containing biospecimen processing and clinical data

Mutation

SNP and Copy Number variation from Affymetrix SNP6

RNA Expression from IlluminaHiseq RNASeqV2

miRNA from IlluminaGA

Methylation from Illumina Infinium Human Methylation450

Reverse Phase Protein Array (RPPA) Expression

Additional Information