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

By Y. Jiao, T. Pawlik, Robert A. Anders, Florin M. Selaru, M. Streppel, Donald J. Lucas, N. Niknafs, Violeta Beleva Guthrie, A. Maitra, P. Argani and 26 more. Nature Genetics, 2013

628 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Oncology, Surgery

View Paper: https://www.semanticscholar.org/paper/dae8e512851c9ab5cc196b4bd1043e36e851aec3

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Citations in the corpus

• Cholangiocarcinoma — evolving concepts and therapeutic strategies (2017, positive): “The recurrent, inactivating mutations in chromatin regulators, including BAP1 , ARID1A , ARID1B , ARID2 , PBRM1, SMARCA2 , SMARCA4 , and SMARCAD1 , support the notion that cholangiocarcinoma has an epigenetically­inclined mutational spectrum 92,122,134,135 .”
• Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma (2017, background): “Our analysis revealed four potentially new CCA driver genes not highlighted in previous CCA publications (6-8,13-17) - RASA1, STK11, MAP2K4, and SF3B1.”
• Human Primary Liver Cancer -derived Organoid Cultures for disease modelling and drug screening (2017, positive): “Notably, we found nonsense mutations (frameshifts or 368 stop-gains) in the chromatin remodelling genes ARID1A (HCC-3 and CC-1), ARID2 (HCC-3) 369 and BAP1 (CHC-1), in agreement with previous reports that have highlighted the importance 370 of these genes in both types of primary liver cancers [56, ”
• Cholangiocarcinoma 2020: the next horizon in mechanisms and management (2020, neutral): “Besides epigenetic silencing, inactivating mutations in multiple chromatin-remodelling genes (including BAP1 , ARID1A and PBRM1 ) are common in iCCA 151 .”
• Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. (2014, background): “These studies highlight the role of chromatin modifiers especially BAP1 in the genetic pathogenesis of this disease [85,86].”