Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2013-12

AUTHORS

Waraporn Chan-on, Maarja-Liisa Nairismägi, 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

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. More... »

PAGES

1474-1478

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.2806

DOI

http://dx.doi.org/10.1038/ng.2806

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1048130718

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24185513


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