Exome sequencing of liver fluke-associated cholangiocarcinoma

被引：397

作者：

Ong, Choon Kiat ^{[2
,3
]}

Subimerb, Chutima ^{[1
,2
,3
]}

Pairojkul, Chawalit ^{[1
]}

Wongkham, Sopit ^{[1
]}

Cutcutache, Ioana ^{[4
]}

Yu, Willie ^{[2
,3
,5
]}

McPherson, John R. ^{[4
]}

Allen, George E. ^{[2
,3
]}

Ng, Cedric Chuan Young ^{[2
,3
]}

Wong, Bernice Huimin ^{[2
,3
]}

Myint, Swe Swe ^{[2
,3
]}

Rajasegaran, Vikneswari ^{[2
,3
]}

Heng, Hong Lee ^{[2
,3
]}

Gan, Anna ^{[2
,3
]}

Zang, Zhi Jiang ^{[3
,6
]}

Wu, Yingting ^{[4
,7
]}

Wu, Jeanie ^{[3
]}

Lee, Ming Hui ^{[3
]}

Huang, DaChuan ^{[2
,3
]}

Ong, Pauline ^{[2
,3
]}

Chan-on, Waraporn ^{[1
,2
,3
]}

Cao, Yun ^{[8
]}

Qian, Chao-Nan ^{[8
]}

Lim, Kiat Hon ^{[9
]}

Ooi, Aikseng ^{[10
]}

Dykema, Karl ^{[10
]}

Furge, Kyle ^{[10
]}

Kukongviriyapan, Veerapol ^{[1
]}

Sripa, Banchob ^{[1
]}

Wongkham, Chaisiri ^{[1
]}

Yongvanit, Puangrat ^{[1
]}

Futreal, P. Andrew ^{[11
]}

Bhudhisawasdi, Vajarabhongsa ^{[1
]}

Rozen, Steve ^{[4
]}

Tan, Patrick ^{[3
,12
,13
]}

Teh, Bin Tean ^{[2
,3
]}

机构：

[1] Khon Kaen Univ, Fac Med, Liver Fluke & Cholangiocarcinoma Res Ctr, Khon Kaen, Thailand

[2] Natl Canc Ctr, Div Med Sci, Nat Canc Ctr Singapore Van Andel Res Inst Transla, Singapore, Singapore

[3] Duke Natl Univ Singapore NUS Grad Med Sch, Div Canc & Stem Cell Biol, Singapore, Singapore

[4] Duke NUS Grad Med Sch, Div Neurosci & Behav Disorders, Singapore, Singapore

[5] NUS Grad Sch Integrat Sci & Engn, Singapore, Singapore

[6] Natl Canc Ctr, Div Cellular & Mol Res, Singapore, Singapore

[7] Singapore MIT Alliance, Singapore, Singapore

[8] Sun Yat Sen Univ Canc Ctr, Guangzhou, Guangdong, Peoples R China

[9] Singapore Gen Hosp, Dept Pathol, Singapore 0316, Singapore

[10] Van Andel Res Inst, Lab Computat Biol, Grand Rapids, MI USA

[11] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton, England

[12] NUS, Canc Sci Inst Singapore, Singapore, Singapore

[13] Genome Inst Singapore, Singapore, Singapore

来源：

NATURE GENETICS | 2012年 / 44卷 / 06期

基金：

英国医学研究理事会;

关键词：

BILIARY-TRACT; GENOMIC ANALYSES; COPY NUMBERS; CANCER; MUTATIONS; CARCINOMA; INSTABILITY; INDUCTION; GROWTH; CELLS;

D O I：

10.1038/ng.2273

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：690 / U113

页数：6

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