Integrative genomic analysis of cholangiocarcinoma identifies distinct IDH-mutant molecular profiles Journal Article


Authors: Farshidfar, F.; Zheng, S.; Gingras, M. C.; Newton, Y.; Shih, J.; Robertson, A. G.; Hinoue, T.; Hoadley, K. A.; Gibb, E. A.; Roszik, J.; Covington, K. R.; Wu, C. C.; Shinbrot, E.; Stransky, N.; Hegde, A.; Yang, J. D.; Reznik, E.; Sadeghi, S.; Pedamallu, C. S.; Ojesina, A. I.; Hess, J. M.; Auman, J. T.; Rhie, S. K.; Bowlby, R.; Borad, M. J.; Zhu, A. X.; Stuart, J. M.; Sander, C.; Akbani, R.; Cherniack, A. D.; Deshpande, V.; Mounajjed, T.; Foo, W. C.; Torbenson, M. S.; Kleiner, D. E.; Laird, P. W.; Wheeler, D. A.; McRee, A. J.; Bathe, O. F.; Andersen, J. B.; Bardeesy, N.; Roberts, L. R.; Kwong, L. N.
Article Title: Integrative genomic analysis of cholangiocarcinoma identifies distinct IDH-mutant molecular profiles
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. © 2017 The Authors
Keywords: dna methylation; cholangiocarcinoma; idh; tcga; arid1a; rna sequencing; whole exome; integrative genomics; lncrnas; multi-omics
Journal Title: Cell Reports
Volume: 18
Issue: 11
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2017-03-14
Start Page: 2780
End Page: 2794
Language: English
DOI: 10.1016/j.celrep.2017.02.033
PROVIDER: scopus
PUBMED: 28297679
PMCID: PMC5493145
DOI/URL:
Notes: Article -- Export Date: 3 April 2017 -- Source: Scopus
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MSK Authors
  1. Chris Sander
    196 Sander
  2. Eduard Reznik
    36 Reznik