title: Exome sequencing of liver fluke-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.
authors.affiliation: National Cancer Centre Singapore-Van Andel Research Institute Translational Research Laboratory, Division of Medical Sciences, Singapore.
authors.forename: Choon Kiat
authors.initials: CK
authors.lastname: Ong
authors.forename: Chutima
authors.initials: C
authors.lastname: Subimerb
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
authors.forename: Sopit
authors.initials: S
authors.lastname: Wongkham
authors.forename: Ioana
authors.initials: I
authors.lastname: Cutcutache
authors.forename: Willie
authors.initials: W
authors.lastname: Yu
authors.forename: John R
authors.initials: JR
authors.lastname: McPherson
authors.forename: George E
authors.initials: GE
authors.lastname: Allen
authors.forename: Cedric Chuan Young
authors.initials: CC
authors.lastname: Ng
authors.forename: Bernice Huimin
authors.initials: BH
authors.lastname: Wong
authors.forename: Swe Swe
authors.initials: SS
authors.lastname: Myint
authors.forename: Vikneswari
authors.initials: V
authors.lastname: Rajasegaran
authors.forename: Hong Lee
authors.initials: HL
authors.lastname: Heng
authors.forename: Anna
authors.initials: A
authors.lastname: Gan
authors.forename: Zhi Jiang
authors.initials: ZJ
authors.lastname: Zang
authors.forename: Yingting
authors.initials: Y
authors.lastname: Wu
authors.forename: Jeanie
authors.initials: J
authors.lastname: Wu
authors.forename: Ming Hui
authors.initials: MH
authors.lastname: Lee
authors.forename: DaChuan
authors.initials: D
authors.lastname: Huang
authors.forename: Pauline
authors.initials: P
authors.lastname: Ong
authors.forename: Waraporn
authors.initials: W
authors.lastname: Chan-on
authors.forename: Yun
authors.initials: Y
authors.lastname: Cao
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
authors.forename: Kiat Hon
authors.initials: KH
authors.lastname: Lim
authors.forename: Aikseng
authors.initials: A
authors.lastname: Ooi
authors.forename: Karl
authors.initials: K
authors.lastname: Dykema
authors.forename: Kyle
authors.initials: K
authors.lastname: Furge
authors.forename: Veerapol
authors.initials: V
authors.lastname: Kukongviriyapan
authors.forename: Banchob
authors.initials: B
authors.lastname: Sripa
authors.forename: Chaisiri
authors.initials: C
authors.lastname: Wongkham
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
authors.forename: P Andrew
authors.initials: PA
authors.lastname: Futreal
authors.forename: Vajarabhongsa
authors.initials: V
authors.lastname: Bhudhisawasdi
authors.forename: Steve
authors.initials: S
authors.lastname: Rozen
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000469:parasitology*; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000469:parasitology*; D004268:DNA-Binding Proteins / Q000235:genetics; D059472:Exome; D005211:Fascioliasis / Q000150:complications*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011971:Receptors, Immunologic / Q000235:genetics; D017422:Sequence Analysis, DNA; D000097905:Roundabout Proteins
chemical_list: D004268:DNA-Binding Proteins; D011971:Receptors, Immunologic; C452979:KMT2C protein, human; C498890:ROBO2 protein, human; D000097905:Roundabout Proteins