Epigenetic DNA hypermethylation in cholangiocarcinoma: Potential roles in pathogenesis, diagnosis and identification of treatment targets

Dalbir S. Sandhu, Abdirashid M. Shire, Lewis Rowland Roberts

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Cholangiocarcinomas (CCs) are highly lethal malignant tumours arising from the biliary tract epithelium. The disease is notoriously difficult to diagnose and is usually fatal because of its typically late clinical presentation and the lack of effective non-surgical therapeutic modalities. The overall survival rate, including resected patients is poor, with less than 5% of patients surviving 5 years, a rate which has not changed significantly over the past 30 years. Although CC is a relatively uncommon tumor, interest in this disease is rising as incidence and mortality rates for intrahepatic cholangiocarcinoma are increasing markedly worldwide. A variety of risk factors, including primary sclerosing cholangitis, liver fluke infestation, and hepatolithiasis have been described. However, for most CCs the cause is unknown, and affected individuals have no history of exposure to, or association with, known risk factors. Recent advances in molecular pathogenesis have highlighted the importance of epigenetic alterations in the form of promoter region hypermethylation and histone deacetylation in addition to genetic changes in the process of cholangiocarcinogenesis. This review provides a comprehensive overview of the genes reported to be methylated in CC to date and their putative roles in cholangiocarcinogenesis. Future directions in the study of methylated genes and their potential roles as diagnostic and prognostic markers are also discussed.

Original languageEnglish (US)
Pages (from-to)12-27
Number of pages16
JournalLiver International
Volume28
Issue number1
DOIs
StatePublished - Jan 2008

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Keywords

  • Cholangiocarcinoma
  • Epigenetics
  • Histone deacetylation
  • Promoter region hypermethylation

ASJC Scopus subject areas

  • Hepatology

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