@article{07d60aa7829e41bb990490f8415c8913,
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.",
keywords = "ARID1A, DNA methylation, IDH, RNA sequencing, TCGA, cholangiocarcinoma, integrative genomics, lncRNAs, multi-omics, whole exome",
author = "CONSORTIA and Farshad Farshidfar and Siyuan Zheng and Gingras, {Marie Claude} and Yulia Newton and Juliann Shih and Robertson, {A. Gordon} and Toshinori Hinoue and Hoadley, {Katherine A.} and Gibb, {Ewan A.} and Jason Roszik and Covington, {Kyle R.} and Wu, {Chia Chin} and Eve Shinbrot and Nicolas Stransky and Apurva Hegde and Yang, {Ju Dong} and Ed Reznik and Sara Sadeghi and Pedamallu, {Chandra Sekhar} and Ojesina, {Akinyemi I.} and Hess, {Julian M.} and Auman, {J. Todd} and Rhie, {Suhn K.} and Reanne Bowlby and Borad, {Mitesh J.} and Zhu, {Andrew X.} and Stuart, {Josh M.} and Chris Sander and Rehan Akbani and Cherniack, {Andrew D.} and Vikram Deshpande and Taofic Mounajjed and Foo, {Wai Chin} and Torbenson, {Michael S.} and Kleiner, {David E.} and Laird, {Peter W.} and Wheeler, {David A.} and McRee, {Autumn J.} and Bathe, {Oliver F.} and Andersen, {Jesper B.} and Nabeel Bardeesy and Roberts, {Lewis R.} and Kwong, {Lawrence N.} and Allotey, {Loretta K.} and Adrian Ally and Domenico Alvaro and Li Ding and Fulton, {Lucinda A.} and Fulton, {Robert S.}",
note = "Funding Information: We are grateful to all the patients and families who contributed to this study. We thank Ina Felau for project management. This work was supported by the following grants from NIH: U54 HG003273, U54 HG003067, U54 HG003079, U24 CA143799, U24 CA143835, U24 CA143840, U24 CA143843, U24 CA143845, U24 CA143848, U24 CA143858, U24 CA143866, U24 CA143867, U24 CA143882, U24 CA143883, U24 CA144025, P30 CA016672, and by the generosity of The Cholangiocarcinoma Foundation. Publisher Copyright: {\textcopyright} 2017 The Authors",
year = "2017",
month = mar,
day = "14",
doi = "10.1016/j.celrep.2017.02.033",
language = "English",
volume = "18",
pages = "2780--2794",
journal = "Cell Reports",
issn = "2639-1856",
number = "11",
}