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Start Over Author "Bernice Huimin Wong" Topic cholangiocarcinoma
2 results on '"Bernice Huimin Wong"'

1. Exome sequencing identifies distinct mutational patterns in liver fluke–related and non-infection-related bile duct cancers

Author

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, and Hong Lee Heng

Subjects
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
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.

Published
2013

2. Exome sequencing of liver fluke–associated cholangiocarcinoma

Author

Karl Dykema, Sopit Wongkham, Chao Nan Qian, George E. Allen, Dachuan Huang, Bin Tean Teh, P. Andrew Futreal, Chaisiri Wongkham, Willie Yu, Chutima Subimerb, Banchob Sripa, Vajarabhongsa Bhudhisawasdi, Puangrat Yongvanit, Choon Kiat Ong, Chawalit Pairojkul, Vikneswari Rajasegaran, Aikseng Ooi, Jeanie Wu, Yun Cao, John R. McPherson, Anna Gan, Patrick Tan, Steve Rozen, Swe Swe Myint, Zhi Jiang Zang, Ioana Cutcutache, Veerapol Kukongviriyapan, Pauline Ong, Kyle A. Furge, Cedric Chuan Young Ng, Bernice Huimin Wong, Yingting Wu, Waraporn Chan-on, Kiat Hon Lim, Hong Lee Heng, and Ming Hui Lee

Subjects
Adult, Male, Fascioliasis, Loss of Heterozygosity, Biology, medicine.disease_cause, Bile duct cancer, Cholangiocarcinoma, Loss of heterozygosity, symbols.namesake, parasitic diseases, Genetics, medicine, GNAS complex locus, Humans, Exome, Receptors, Immunologic, Exome sequencing, Aged, Sanger sequencing, Mutation, fungi, Sequence Analysis, DNA, Middle Aged, medicine.disease, DNA-Binding Proteins, Bile Duct Neoplasms, Cancer research, biology.protein, symbols, Female, KRAS
Abstract

Bin Tean Teh and colleagues report exome sequencing of Opisthorchis viverrini–related cholangiocarcinoma, a fatal bile duct cancer associated with liver fluke infection. Opisthorchis viverrini–related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini–related tumors and matched normal tissue. We identified and validated 206 somatic mutations in 187 genes using Sanger sequencing and selected 15 genes for mutation prevalence screening in an additional 46 individuals with CCA (cases). In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8–3.7% of cases. These included inactivating mutations in MLL3 (in 14.8% of cases), ROBO2 (9.3%), RNF43 (9.3%) and PEG3 (5.6%), and activating mutations in the GNAS oncogene (9.3%). These genes have functions that can be broadly grouped into three biological classes: (i) deactivation of histone modifiers, (ii) activation of G protein signaling and (iii) loss of genome stability. This study provides insight into the mutational landscape contributing to O. viverrini–related CCA.

Published
2012

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