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 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

doi:10.1038/ng.2273

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

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

408 Scopus citations

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 language	English
Pages (from-to)	690-693
Number of pages	4
Journal	Nature Genetics
Volume	44
Issue number	6
DOIs	https://doi.org/10.1038/ng.2273
State	Published - 06 2012
Externally published	Yes

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Ong, C. K., Subimerb, C., Pairojkul, C., Wongkham, S., Cutcutache, I., Yu, W., McPherson, J. R., Allen, G. E., Ng, C. C. Y., Wong, B. H., Myint, S. S., Rajasegaran, V., Heng, H. L., Gan, A., Zang, Z. J., Wu, Y., Wu, J., Lee, M. H., Huang, D., ... Teh, B. T. (2012). Exome sequencing of liver flukeg-associated cholangiocarcinoma. Nature Genetics, 44(6), 690-693. https://doi.org/10.1038/ng.2273

@article{d28ee3d8382440089ebe049143503520,

title = "Exome sequencing of liver flukeg-associated cholangiocarcinoma",

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.",

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

year = "2012",

month = jun,

doi = "10.1038/ng.2273",

language = "英语",

volume = "44",

pages = "690--693",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "6",

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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

TY - JOUR

T1 - Exome sequencing of liver flukeg-associated cholangiocarcinoma

AU - Ong, Choon Kiat

AU - Subimerb, Chutima

AU - Pairojkul, Chawalit

AU - Wongkham, Sopit

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

AU - Rajasegaran, Vikneswari

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

PY - 2012/6

Y1 - 2012/6

N2 - 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.

AB - 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.

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U2 - 10.1038/ng.2273

DO - 10.1038/ng.2273

M3 - 文章

C2 - 22561520

AN - SCOPUS:84861581233

SN - 1061-4036

VL - 44

SP - 690

EP - 693

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

Exome sequencing of liver flukeg-associated cholangiocarcinoma

Abstract

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