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Home > Publications > Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles, 2017

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

Cell Reports: Volume 18, Issue 11, p2780 - 2794

DOI: http://dx.doi.org/10.1016/j.celrep.2017.02.033

Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

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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.

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Mutations

Reverse Phase Protein Array (RPPA) Expression

RNA Expression from IlluminaHiseq RNASeq

SNP and Copy Number variation from Affymetrix SNP6 and IlluminaHiSeq Low Pass Whole Genome sequencing

miRNA from Illumina HiSeq

Methylation from Illumina Infinium Human Methylation450

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