Abstract 5184: Distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers revealed by whole exome sequencing

Abstract

Cholangiocarcinoma, the second most common liver cancer, is known to be caused by different etiologies such as liver fluke infection, choledochal cyst and primary sclerosing cholangitis. Thus, this cancer provides a good model to study the impact of different carcinogenic exposures on the specific patterns of somatic mutations in human tumors. To address this issue, we profiled 209 cholangiocarcinomas (CCAs) from Asia and Europe, including 108 cases caused by liver fluke Opisthorchis viverrini (O. viverrini)-infection and 101 cases due to non-O. viverrini etiologies. Whole-exome (N = 15) and prevalence screening (N = 194) revealed recurrent somatic mutations in BAP1 and ARID1A, neither of which has been previously reported to be mutated in CCA. Comparisons between intrahepatic O. viverrini and non-O. viverrini CCAs demonstrated statistically significant different mutation patterns: BAP1 and IDH1/2 were more frequently mutated in non-O. viverrini CCAs, while TP53 displayed the reciprocal pattern. Functional studies demonstrated tumor suppressive roles of BAP1 and ARID1A, establishing the role of chromatin modulators in CCA pathogenesis. These findings indicate that different causative etiologies may induce distinct somatic alterations even within the same tumor type.

Citation Format: Choon Kiat Ong, Waraporn Chan-on, Maarja-Liisa Nairismagi, Weng Khong Lim, Simona Dima, Chawalit Pairojkul, Paiboon Sithithaworn, Irinel Popescu, Steve Rozen, Patrick Tan, Bin Tean Teh. Distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers revealed by whole exome sequencing. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5184. doi:10.1158/1538-7445.AM2014-5184