Exome sequencing of liver fluke-associated cholangiocarcinoma.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ong, CK; Subimerb, C; Pairojkul, C; Wongkham, S; Cutcutache, I; Yu, W; McPherson, JR; Allen, GE; Ng, CCY; Wong, BH; Myint, SS; Rajasegaran, V; Heng, HL; Gan, A; Zang, ZJ; Wu, Y; Wu, J; Lee, MH; Huang, D; Ong, P; Chan-on, W; Cao, Y; Qian, C-N; Lim, KH; Ooi, A; Dykema, K; Furge, K; Kukongviriyapan, V; Sripa, B; Wongkham, C; Yongvanit, P; Futreal, PA; Bhudhisawasdi, V; Rozen, S; Tan, P; Teh, BT

Published Date

  • May 6, 2012

Published In

Volume / Issue

  • 44 / 6

Start / End Page

  • 690 - 693

PubMed ID

  • 22561520

Pubmed Central ID

  • 22561520

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/ng.2273


  • eng

Conference Location

  • United States