Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas - PubMed (original) (raw)

. 2013 Dec;45(12):1470-1473.

doi: 10.1038/ng.2813. Epub 2013 Nov 3.

Yuchen Jiao # 1 2 3, Timothy M Pawlik # 3 4, Robert A Anders # 3 5, Florin M Selaru 6, Mirte M Streppel 5, Donald J Lucas 7, Noushin Niknafs 8, Violeta Beleva Guthrie 8, Anirban Maitra 3 5, Pedram Argani 3 5, G Johan A Offerhaus 9, Juan Carlos Roa 10, Lewis R Roberts 11, Gregory J Gores 11, Irinel Popescu 12, Sorin T Alexandrescu 12, Simona Dima 12, Matteo Fassan 13 14, Michele Simbolo 13 14, Andrea Mafficini 13, Paola Capelli 14, Rita T Lawlor 13 14, Andrea Ruzzenente 15, Alfredo Guglielmi 15, Giampaolo Tortora 16, Filippo de Braud 17, Aldo Scarpa 13 14, William Jarnagin 18, David Klimstra 19, Rachel Karchin 8, Victor E Velculescu 1 2 3, Ralph H Hruban 3 5, Bert Vogelstein 1 2 3, Kenneth W Kinzler 1 2 3, Nickolas Papadopoulos 1 2 3, Laura D Wood 5

Affiliations

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

Yuchen Jiao et al. Nat Genet. 2013 Dec.

Abstract

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.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Genes with frequent inactivating mutations in intrahepatic cholangiocarcinoma. Inactivating mutations occurred throughout the coding sequences of BAP1, ARID1A and PBRM1. Rectangles, splice-site mutations; triangles, insertions and deletions; ovals, missense mutations; stars, nonsense mutations. H, HBM-like motif; BR, BRCA1-interacting domain; C, coiled-coil domain; N, nuclear localization signal; LXXLL, LXXLL domain; ARID, ARID domain; BD, bromodomain; BAH, BAH domain; HMG, HMG box.

Comment in

References

    1. Everhart JE, Ruhl CE. Burden of digestive diseases in the United States Part III: Liver, biliary tract, and pancreas. Gastroenterology. 2009;136:1134–1144. - PubMed
    1. Blechacz B, et al. Clinical diagnosis and staging of cholangiocarcinoma. Nat. Rev. Gastroenterol. Hepatol. 2011;8:512–522. - PMC - PubMed
    1. Borger DR, et al. Frequent mutation of isocitrate dehydrogenase IDH1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist. 2012;17:72–79. - PMC - PubMed
    1. Voss JS, et al. Molecular profiling of cholangiocarcinoma shows potential for targeted therapy treatment decisions. Hum. Pathol. 2013;44:1216–1222. - PubMed
    1. Xu RF, et al. KRAS and PIK3CA but not BRAF genes are frequently mutated in Chinese cholangiocarcinoma patients. Biomed. Pharmacother. 2011;65:22–26. - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources