Exome sequencing identifies distinct mutational patterns in liver fluke–related and non-infection-related bile duct cancers
| Autor: | Chawalit Pairojkul, Simona Dima, Puangrat Yongvanit, Peng Chung Cheow, Vikneswari Rajasegaran, Steven G. Rozen, Dachuan Huang, Choon Kiat Ong, Paiboon Sithithaworn, Iain Beehuat Tan, Sopit Wongkham, Weng Khong Lim, Swe Swe Myint, Kiat Hon Lim, Sanjanaa Nagarajan, Irinel Popescu, Ioana Cutcutache, Apinya Jusakul, John R. McPherson, Patrick Tan, Maarja-Liisa Nairismagi, Anca Nastase, Shenli Zhang, Narong Khuntikeo, London L.P.J. Ooi, Vajaraphongsa Bhudhisawasdi, Cedric Chuan Young Ng, Willie Yu, Ser Yee Lee, Alexander Y. F. Chung, Priya Vohra, Bin Tean Teh, Anna Gan, Su Pin Choo, Pierce K. H. Chow, Dan G. Duda, Bernice Huimin Wong, Waraporn Chan-on, Hong Lee Heng |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Fascioliasis Pathology medicine.medical_specialty Bile duct cancer Cholangiocarcinoma Gene Frequency parasitic diseases Tumor Cells Cultured Genetics medicine Animals Humans Fasciola hepatica Exome Genetic Predisposition to Disease Opisthorchis viverrini Exome sequencing BAP1 biology Bile duct Tumor Suppressor Proteins Sequence Analysis DNA Liver fluke biology.organism_classification medicine.disease Isocitrate Dehydrogenase Bile Ducts Intrahepatic medicine.anatomical_structure Bile Duct Neoplasms Mutation Female Liver cancer Ubiquitin Thiolesterase |
| Zdroj: | Nature Genetics. 45:1474-1478 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng.2806 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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