Exome sequencing of liver fluke–associated cholangiocarcinoma
| Autor: | 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, Ming Hui Lee |
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| Rok vydání: | 2012 |
| Předmět: |
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 |
| Zdroj: | Nature Genetics. 44:690-693 |
| ISSN: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng.2273 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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