Genetics of Opisthorchis viverrini-related cholangiocarcinoma

Curr Opin Gastroenterol. 2015 May;31(3):258-63. doi: 10.1097/MOG.0000000000000162.

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bile Duct Neoplasms / genetics*
  • Bile Duct Neoplasms / parasitology
  • Bile Duct Neoplasms / pathology
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / parasitology
  • Cholangiocarcinoma / pathology
  • DNA-Binding Proteins
  • Exome
  • Gene Expression Regulation, Neoplastic / genetics*
  • Genetic Variation
  • Humans
  • Opisthorchis / isolation & purification*
  • Receptors, Immunologic / genetics*
  • Sequence Analysis, DNA
  • Transcriptional Activation / genetics

Substances

  • DNA-Binding Proteins
  • Receptors, Immunologic