Journal Article

Exome sequencing of liver fluke–associated cholangiocarcinoma

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

2012

Overview

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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/208/514/1948 / 631/208/69 / Adult / Aged / Agriculture / Animal Genetics and Genomics / Bile Duct Neoplasms - genetics / Bile Duct Neoplasms - parasitology / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cholangiocarcinoma - genetics / Cholangiocarcinoma - parasitology / DNA-Binding Proteins - genetics / Exome / Exome sequencing / Fascioliasis - complications / Female / Fundamental and applied biological sciences. Psychology / Gastroenterology. Liver. Pancreas. Abdomen / Gene Function / Gene mutations / Genetic engineering / Genetics of eukaryotes. Biological and molecular evolution / Health aspects / Human Genetics / Humans / letter / Liver / Liver cancer / Liver. Biliary tract. Portal circulation. Exocrine pancreas / Loss of Heterozygosity / Male / Medical sciences / Middle Aged / Mutation / Opisthorchis / Parasites / Public health / Receptors, Immunologic - genetics / Sequence Analysis, DNA / Tumors