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

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.…

• CF
  Cholangiocarcinoma Foundation
• SU
  Sapienza Università di Roma
• NI
  National Institutes of Health

  Awards: U24 CA143882, U54 HG003079, U24 CA143866, U54 HG003067, U24 CA143799, U24 CA143835, U24 CA143843, U24 CA144025, P30 CA016672, U54 HG003273, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143883, U24 CA143840, U24 CA143867
• IO
  Institute of Chemistry, Chinese Academy of Sciences