Multistage carcinogenesis in Barrett's esophagus

Cancer Lett. 2007 Jan 8;245(1-2):22-32. doi: 10.1016/j.canlet.2006.03.018. Epub 2006 May 19.


The multistage carcinogenesis of esophageal adenocarcinoma is a process of clonal evolution within Barrett's esophagus neoplasms. The initiating event for Barrett's esophagus is unknown, but is associated with chronic gastric reflux which probably also promotes progression. Inactivation of both alleles of CDKN2A appear to be early events causing clonal expansion. Clones with TP53 inactivated expand if they have already inactivated CDKN2A. After TP53 has been inactivated, tetraploid and aneuploid clones tend to develop. The final events that lead to invasion and metastasis are unknown. Evolutionary biology provides important tools to understand clonal evolution in progression and cancer prevention.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Barrett Esophagus / genetics
  • Barrett Esophagus / pathology*
  • Chronic Disease
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Disease Progression
  • Esophageal Neoplasms / etiology
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology*
  • Gastroesophageal Reflux / complications
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Models, Biological
  • Tumor Suppressor Protein p53 / genetics


  • Cyclin-Dependent Kinase Inhibitor p16
  • Tumor Suppressor Protein p53