Exome sequencing of liver fluke–associated cholangiocarcinoma View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2012-06

AUTHORS

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

ABSTRACT

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. More... »

PAGES

690

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.2273

DOI

http://dx.doi.org/10.1038/ng.2273

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1053156141

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22561520


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