Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas Journal Article
| Authors: | Jiao, Y.; Pawlik, T. M.; Anders, R. A.; Selaru, F. M.; 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.; Mafficini, A.; Capelli, P.; Lawlor, R. T.; Ruzzenente, A.; Guglielmi, A.; Tortora, G.; De Braud, F.; Scarpa, A.; Jarnagin, W.; Klimstra, D.; Karchin, R.; Velculescu, V. E.; Hruban, R. H.; Vogelstein, B.; Kinzler, K. W.; Papadopoulos, N.; Wood, L. D. |
| Article Title: | Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas |
| 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. |
| Keywords: | cancer survival; controlled study; human tissue; gene sequence; somatic mutation; cancer staging; wild type; phosphatidylinositol 3 kinase; protein p53; survival time; regulatory mechanism; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; gene fusion; bile duct carcinoma; oncogene k ras; gallbladder carcinoma; fibroblast growth factor receptor 2; chromatin assembly and disassembly; genetic heterogeneity; isocitrate dehydrogenase 1; smad4 protein; bap1 gene; isocitrate dehydrogenase 1 gene; isocitrate dehydrogenase 2 gene; indel mutation; tp53 gene; cancer prognosis; exome; isocitrate dehydrogenase 2; arid1a gene; smad4 gene; pbrm1 gene; phosphatidylinositol 4,5 bisphosphate 3 kinase; human; priority journal; article; phosphatidylinositol 4 phosphate 3 kinase; exome sequencing; fibroblast growth factor receptor 2 gene; phosphatidylinositol 3 kinase gene; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase gene; phosphatidylinositol 4 phosphate 3 kinase gene; phosphatidylinositol 4,5 bisphosphate 3 kinase gene |
| Journal Title: | Nature Genetics |
| Volume: | 45 |
| Issue: | 12 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2013-12-01 |
| Start Page: | 1470 |
| End Page: | 1473 |
| Language: | English |
| DOI: | 10.1038/ng.2813 |
| PROVIDER: | scopus |
| PUBMED: | 24185509 |
| PMCID: | PMC4013720 |
| DOI/URL: | |
| Notes: | Export Date: 2 January 2014 -- CODEN: NGENE -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work