Genetic and epigenetic abnormalities in primary sclerosing cholangitis-associated cholangiocarcinoma

Inflamm Bowel Dis. 2013 Jul;19(8):1789-97. doi: 10.1097/MIB.0b013e318281f49a.


Primary sclerosing cholangitis (PSC) is a cholestatic liver disease of unknown etiology, characterized by chronic inflammation of the biliary tree with subsequent fibrosis and cirrhosis of the liver. Patients with PSC are at increased risk for the development of cholangiocarcinoma (CCA), a highly malignant epithelial tumor arising from the intrahepatic and extrahepatic bile ducts. Currently, orthotopic liver transplantation is the only curative treatment. The lack of efficient diagnostic methods for early detection and the limited therapeutic options for CCA are major problems and are associated with poor survival. The pathogenesis of PSC-associated CCA is complex and poorly understood. It seems that pro-inflammatory cytokines play an important role in genetic and epigenetic changes that contribute to the carcinogenic process. The mapping of genetic alterations may elucidate molecular targets that may be applied as biomarkers to facilitate early diagnosis of malignant degeneration to improve patient outcome. In the last decade, the introduction of several novel molecular techniques available for genome-wide screening has advanced our knowledge on many of the genetic abnormalities that are prevalent in CCA and PSC-associated CCA. This review summarizes genetic and epigenetic abnormalities, which have important potential for clinical application.

Publication types

  • Review

MeSH terms

  • Bile Duct Neoplasms / etiology*
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic / pathology*
  • Cholangiocarcinoma / etiology*
  • Cholangiocarcinoma / pathology
  • Cholangitis, Sclerosing / complications*
  • Cholangitis, Sclerosing / genetics
  • Cholangitis, Sclerosing / pathology
  • Epigenomics*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans