title: Genetics of Opisthorchis viverrini-related cholangiocarcinoma.
abstract: OBJECTIVE
  We review the genetic, epigenetic and transcriptional landscape of liver fluke (Opisthorchis viverrini, Ov)-related cholangiocarcinoma (CCA). Its distinct alterations, as compared with non-Ov-related CCA may help shed light on its underlying molecular mechanisms.
  
  
  RESULTS
  Recent whole-exome and targeted sequencing not only confirmed frequent mutations in known CCA-related genes including TP53 (44%), KRAS (16.7%) and SMAD4 (16.7%), but also revealed mutations in novel CCA-related genes associated with chromatin remodeling [BAP1 (2.8%), ARID1A (17.6%), MLL3 (13%) and IDH1/2 (2.8%)], WNT signaling [RNF43 (9.3%) and PEG3 (5.6%)] and KRAS/G protein signaling [GNAS (9.3%) and ROBO2 (9.3%)]. Interestingly, there is a significant difference in the frequency of mutated genes between Ov-related CCA and non-Ov-related CCA, such as p53 and IDH1/2, reflecting the impact of cause on pathogenesis. Altered DNA methylation and transcriptional profiles associated with xenobiotic metabolism and pro-inflammatory responses were also found in Ov-related CCA.
  
  
  CONCLUSIONS
  Liver fluke-induced chronic inflammation plays a crucial role in cholangiocarcinogenesis, resulting in distinct signatures of genetic, epigenetic and transcriptional alterations. These alterations, when contrasted with non-Ov-related CCA, indicate a unique pathogenic process in Ov-related CCA and may have potential clinical implications on diagnostics, therapeutics and prevention.
authors.affiliation: aLaboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore bProgram in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore cDepartment of Pharmacology, Faculty of Medicine dLiver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen, Thailand eCancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Apinya
authors.initials: A
authors.lastname: Jusakul
authors.forename: Sarinya
authors.initials: S
authors.lastname: Kongpetch
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000469:parasitology / Q000473:pathology; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000469:parasitology / Q000473:pathology; D004268:DNA-Binding Proteins; D059472:Exome; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D009891:Opisthorchis / Q000302:isolation & purification*; D011971:Receptors, Immunologic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D011971:Receptors, Immunologic