Journal Article

Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas

Gores, Gregory J, Jarnagin, William, Lucas, Donald J, Fassan, Matteo, Popescu, Irinel, Alexandrescu, Sorin T, Argani, Pedram, Selaru, Florin M, Streppel, Mirte M, Scarpa, Aldo, de Braud, Filippo, Papadopoulos, Nickolas, Ruzzenente, Andrea, Maitra, Anirban, Velculescu, Victor E, Anders, Robert A, Tortora, Giampaolo, Hruban, Ralph H, Guglielmi, Alfredo, Guthrie, Violeta Beleva, Pawlik, Timothy M, Wood, Laura D, Mafficini, Andrea, Klimstra, David, Jiao, Yuchen, Vogelstein, Bert, Karchin, Rachel, Roa, Juan Carlos, Dima, Simona, Offerhaus, G Johan A, Capelli, Paola, Niknafs, Noushin, Simbolo, Michele, Roberts, Lewis R, Lawlor, Rita T, Kinzler, Kenneth W

2013

Overview

Laura Wood, Kenneth Kinzler, Nickolas Papadopoulos, Aldo Scarpa and colleagues report exome sequencing of intrahepatic cholangiocarcinomas. They identify recurrent somatic mutations in BAP1 , ARID1A and PBRM1 . Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin-remodeling genes (including BAP1 , ARID1A and PBRM1 ), and mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in the IDH1 and IDH2 genes encoding metabolic enzymes in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These discoveries highlight the key role of dysregulated chromatin remodeling in intrahepatic cholangiocarcinomas.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 45 / 45/23 / 45/47 / 692/308/2056 / 692/308/575 / 692/699/67/1504/1329/1326 / 692/699/67/1504/1329/1499 / Agriculture / Animal Genetics and Genomics / Bile Duct Neoplasms / Bile Ducts, Intrahepatic / Biomedicine / Cancer Research / Cholangiocarcinoma - epidemiology / Cholangiocarcinoma - genetics / Cohort Studies / Exome - genetics / Exome sequencing / Female / Gene Frequency / Gene Function / Gene mutations / Genes / Human Genetics / Humans / Identification and classification / letter / Liver Neoplasms - epidemiology / Liver Neoplasms - genetics / Male / Medical research / Methods / Mutation / Mutation, Missense / Nuclear Proteins - genetics / Sequence Analysis, DNA / Studies / Survival Analysis / Transcription Factors - genetics / Tumor Suppressor Proteins - genetics / Ubiquitin Thiolesterase - genetics