Exome Sequencing Identifies Distinct Mutational Patterns in Liver Fluke-related and Non-infection-related Bile Duct Cancers

Overview

Journal Nat Genet

Specialty Genetics

Date 2013 Nov 5

PMID 24185513

Citations 238

Authors

Waraporn Chan-On

Maarja-Liisa Nairismagi

Choon Kiat Ong

Weng Khong Lim

Simona Dima

Chawalit Pairojkul

Kiat Hon Lim

John R McPherson

Ioana Cutcutache

Hong Lee Heng

London Ooi

Alexander Chung

Pierce Chow

Peng Chung Cheow

Ser Yee Lee

Su Pin Choo

Iain Bee Huat Tan

Dan Duda

Anca Nastase

Swe Swe Myint

Bernice Huimin Wong

Anna Gan

Vikneswari Rajasegaran

Cedric Chuan Young Ng

Sanjanaa Nagarajan

Apinya Jusakul

Shenli Zhang

Priya Vohra

Willie Yu

DaChuan Huang

Paiboon Sithithaworn

Puangrat Yongvanit

Sopit Wongkham

Narong Khuntikeo

Vajaraphongsa Bhudhisawasdi

Irinel Popescu

Steven G Rozen

Patrick Tan

Bin Tean Teh

Affiliations

Soon will be listed here.

Abstract

The impact of different carcinogenic exposures on the specific patterns of somatic mutation in human tumors remains unclear. To address this issue, we profiled 209 cholangiocarcinomas (CCAs) from Asia and Europe, including 108 cases caused by infection with the liver fluke Opisthorchis viverrini and 101 cases caused by non-O. viverrini-related etiologies. Whole-exome sequencing (n = 15) and prevalence screening (n = 194) identified recurrent somatic mutations in BAP1 and ARID1A, neither of which, to our knowledge, has previously been reported to be mutated in CCA. Comparisons between intrahepatic O. viverrini-related and non-O. viverrini-related CCAs demonstrated statistically significant differences in mutation patterns: BAP1, IDH1 and IDH2 were more frequently mutated in non-O. viverrini CCAs, whereas TP53 mutations showed the reciprocal pattern. Functional studies demonstrated tumor suppressive functions for 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.

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