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

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

Research output: Contribution to journalArticle


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.

Original languageEnglish (US)
Pages (from-to)1470-1473
Number of pages4
JournalNature Genetics
Issue number12
StatePublished - Dec 2013


ASJC Scopus subject areas

  • Genetics

Cite this

Jiao, Y., Pawlik, T. M., Anders, R. A., Selaru, F., Streppel, M. M., Lucas, D. J., Niknafs, N., Guthrie, V. B., Maitra, A., Argani, P., Offerhaus, G. J. A., Roa, J. C., Roberts, L. R., Gores, G. J., Popescu, I., Alexandrescu, S. T., Dima, S., Fassan, M., Simbolo, M., ... Wood, L. D. (2013). Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas. Nature Genetics, 45(12), 1470-1473. https://doi.org/10.1038/ng.2813