Exome sequencing of liver flukeg-associated cholangiocarcinoma

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 OngWaraporn 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

Research output: Contribution to journalArticle

247 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)690-693
Number of pages4
JournalNature Genetics
Volume44
Issue number6
DOIs
StatePublished - Jun 2012
Externally publishedYes

Fingerprint

Exome
Cholangiocarcinoma
Opisthorchis
Mutation
Liver
Genes
Bile Duct Neoplasms
Genomic Instability
Neoplasm Genes
Oncogenes
GTP-Binding Proteins
Histones
Parasites
Public Health
Neoplasms

ASJC Scopus subject areas

  • Genetics

Cite this

Ong, C. K., Subimerb, C., Pairojkul, C., Wongkham, S., Cutcutache, I., Yu, W., ... Teh, B. T. (2012). Exome sequencing of liver flukeg-associated cholangiocarcinoma. Nature Genetics, 44(6), 690-693. https://doi.org/10.1038/ng.2273

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

In: Nature Genetics, Vol. 44, No. 6, 06.2012, p. 690-693.

Research output: Contribution to journalArticle

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, CN, 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 2012, 'Exome sequencing of liver flukeg-associated cholangiocarcinoma', Nature Genetics, vol. 44, no. 6, pp. 690-693. https://doi.org/10.1038/ng.2273
Ong CK, Subimerb C, Pairojkul C, Wongkham S, Cutcutache I, Yu W et al. Exome sequencing of liver flukeg-associated cholangiocarcinoma. Nature Genetics. 2012 Jun;44(6):690-693. https://doi.org/10.1038/ng.2273
Ong, Choon Kiat ; Subimerb, Chutima ; Pairojkul, Chawalit ; Wongkham, Sopit ; Cutcutache, Ioana ; Yu, Willie ; McPherson, John R. ; Allen, George E. ; Ng, Cedric Chuan Young ; Wong, Bernice Huimin ; Myint, Swe Swe ; Rajasegaran, Vikneswari ; Heng, Hong Lee ; Gan, Anna ; Zang, Zhi Jiang ; Wu, Yingting ; Wu, Jeanie ; Lee, Ming Hui ; Huang, Dachuan ; Ong, Pauline ; Chan-On, Waraporn ; Cao, Yun ; Qian, Chao Nan ; Lim, Kiat Hon ; Ooi, Aikseng ; Dykema, Karl ; Furge, Kyle ; Kukongviriyapan, Veerapol ; Sripa, Banchob ; Wongkham, Chaisiri ; Yongvanit, Puangrat ; Futreal, P. Andrew ; Bhudhisawasdi, Vajarabhongsa ; Rozen, Steve ; Tan, Patrick ; Teh, Bin Tean. / Exome sequencing of liver flukeg-associated cholangiocarcinoma. In: Nature Genetics. 2012 ; Vol. 44, No. 6. pp. 690-693.
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AU - Ong, Choon Kiat

AU - Subimerb, Chutima

AU - Pairojkul, Chawalit

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AU - Cutcutache, Ioana

AU - Yu, Willie

AU - McPherson, John R.

AU - Allen, George E.

AU - Ng, Cedric Chuan Young

AU - Wong, Bernice Huimin

AU - Myint, Swe Swe

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AU - Heng, Hong Lee

AU - Gan, Anna

AU - Zang, Zhi Jiang

AU - Wu, Yingting

AU - Wu, Jeanie

AU - Lee, Ming Hui

AU - Huang, Dachuan

AU - Ong, Pauline

AU - Chan-On, Waraporn

AU - Cao, Yun

AU - Qian, Chao Nan

AU - Lim, Kiat Hon

AU - Ooi, Aikseng

AU - Dykema, Karl

AU - Furge, Kyle

AU - Kukongviriyapan, Veerapol

AU - Sripa, Banchob

AU - Wongkham, Chaisiri

AU - Yongvanit, Puangrat

AU - Futreal, P. Andrew

AU - Bhudhisawasdi, Vajarabhongsa

AU - Rozen, Steve

AU - Tan, Patrick

AU - Teh, Bin Tean

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