Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct  IDH -Mutant Molecular Profiles
Creators: name: Kasaian, Katayoon
name: Veluvolu, Umadevi
name: Berrios, Mario
name: Kleiner, David E.
name: Tan, Donghui
name: Gardner, Johanna
name: Cherniack, Andrew D.
name: Bowlby, Reanne
name: Shinbrot, Eve
name: Parker, Joel S.
name: Deshpande, Vikram
name: Mungall, Andrew J.
name: O’Brien, Daniel R.
name: Farshidfar, Farshad
name: Laird, Peter W.
name: Yang, Ju Dong
name: Jones, Steven J.M.
name: Roach, Jeffrey
name: Chandan, Vishal C.
name: Foo, Wai Chin
name: Weinstein, John N.
name: Liu, Wenbin
name: Ojesina, Akinyemi I.
name: Hinoue, Toshinori
name: Perou, Amy H.
name: Wu, Chia-Chin
name: Leraas, Kristen M.
name: Auman, J. Todd
name: Arora, Arshi
name: Lai, Phillip H.
name: Skelly, Tara
name: Zenklusen, Jean C.
name: Holbrook, Andrea
name: Giama, Nasra H.
name: Wang, Zhining
name: Mills, Gordon B.
name: Gibbs, Richard A.
name: Zmuda, Erik
name: Reznik, Ed
name: Demchok, John A.
name: Xi, Liu
name: Wu, Ye
name: Tam, Angela
name: Hegde, Apurva M.
name: Chuah, Eric
name: Stoppler, Hubert
name: Covington, Kyle R.
name: Bowen, Jay
name: Carpino, Guido
name: Robertson, A. Gordon
name: Zhu, Andrew X.
name: Hayes, D. Neil
name: Pihl, Todd
name: Cordes, Matthew G.
name: Naresh, Rashi
name: Cardinale, Vincenzo
name: Huang, Mei
name: Rathmell, W. Kimryn
name: Gingras, Marie-Claude
name: Mayo, Michael
name: Zhang, Jiashan (Julia)
name: Shen, Ronglai
name: Bathe, Oliver F.
name: Wheeler, David A.
name: Ma, Yussanne
name: Patel, Tushar C.
name: Murray, Bradley A.
name: Fulton, Lucinda A.
name: Matsushita, Marcus M.
name: Chaiteerakij, Roongruedee
name: Crain, Daniel
name: Wilson, Richard K.
name: Shelton, Candace
name: Schumacher, Steven E.
name: Moore, Richard A.
name: Gaudio, Eugenio
name: Paulauskis, Joseph
name: De Rose, Agostino Maria
name: Carvalho, Andre L.
name: Roberts, Lewis R.
name: Lawrence, Michael S.
name: Wong, Tina
name: Bardeesy, Nabeel
name: Mallery, David
name: Chin, Lynda
name: Soloway, Matthew G.
name: Simons, Janae V.
name: Bodenheimer, Tom
name: Jones, Corbin D.
name: Morris, Scott
name: Genovese, Giannicola
name: Kim, Jaegil
name: Andersen, Jesper B.
name: Appelbaum, Elizabeth L.
name: Shroff, Rachna
name: Thiessen, Nina
name: Alvaro, Domenico
name: Brooks, Denise
name: Sun, Qiang
name: Schein, Jacqueline E.
name: Sofia, Heidi J.
name: Evason, Kimberley
name: Weisenberger, Daniel J.
name: Allotey, Loretta K.
name: Bootwalla, Moiz S.
name: Fulton, Robert S.
name: Marra, Marco A.
name: Beroukhim, Rameen
name: Sheth, Margi
name: Pedamallu, Chandra Sekhar
name: Lu, Yiling
name: Boice, Lori
name: Hoadley, Katherine A.
name: Bathe, Oliver F.
name: Noble, Michael S.
name: Grazi, Gian Luca
name: Kocher, Jean-Pierre A.
name: Ally, Adrian
name: Kwong, Lawrence N.
name: Meng, Shaowu
name: Moser, Catherine D.
name: Gibb, Ewan A.
name: Hutter, Carolyn M.
name: Zheng, Siyuan
name: Shi, Yan
name: McLellan, Michael D.
name: Giuliante, Felice
name: Van Den Berg, David J.
name: Ramirez, Nilsa C.
name: Thorne, Leigh B.
name: Sander, Chris
name: McRee, Autumn J.
name: Bragazzi, Maria Consiglia
name: Getz, Gad
name: Mose, Lisle E.
name: Zhang, Hailei
name: Ding, Li
name: Shih, Juliann
name: Tarnuzzer, Roy
name: Rhie, Suhn K.
name: Meier, Sam
name: Baylin, Stephen B.
name: Cho, Juok
name: Miller, Christopher A.
name: Felau, Ina
name: Mieczkowski, Piotr A.
name: Shelton, Troy
name: Cibulskis, Carrie
name: Schmidt, Heather K.
name: Borad, Mitesh J.
name: Balu, Saianand
name: Jefferys, Stuart R.
name: Ferguson, Martin L.
name: Saksena, Gordon
name: Mardis, Elaine R.
name: Sadeghi, Sara
name: Hoyle, Alan P.
name: Frazer, Scott
name: Stransky, Nicolas
name: Carlsen, Rebecca
name: Roszik, Jason
name: Wan, Yunhu
name: Defreitas, Timothy
name: Mounajjed, Taofic
name: Fronick, Catrina C.
name: Balasundaram, Miruna
name: Zheng, Siyuan
name: Gabriel, Stacey B.
name: Penny, Robert
name: Yang, Liming
name: Newton, Yulia
name: Perou, Charles M.
name: Lin, Pei
name: Holt, Robert A.
name: Chudamani, Sudha
name: Auman, J. Todd
name: Farshidfar, Farshad
name: Radenbaugh, Amie J.
name: Mungall, Karen
name: Stuart, Josh
name: Kelley, Robin K.
name: Curley, Erin
name: Lolla, Laxmi
name: Verhaak, Roel G.W.
name: Liu, Jia
name: Dhalla, Noreen
name: Heiman, David I.
name: Gehlenborg, Nils
name: Choe, Gina
name: Wise, Lisa
name: Gerken, Mark
name: Franchitto, Antonio
name: Gastier-Foster, Julie M.
name: Lichtenberg, Tara M.
name: Akbani, Rehan
name: Hess, Julian M.
name: Torbenson, Michael S.
name: Meyerson, Matthew
name: Voet, Doug
name: Sipahimalani, Payal
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2017

description: 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.