[Epigenetic alterations in colorectal carcinomas and precancerous lesions]

Z Gastroenterol. 2008 Oct;46(10):1202-6. doi: 10.1055/s-2008-1027406. Epub 2008 Oct 20.
[Article in German]

Abstract

Colorectal carcinomas are the third most common malignant tumours worldwide with an incidence of 570,000 per year. According to their molecular mechanisms, sporadic colorectal carcinomas can be divided into two different phenotypes. The genetic phenotype, 50 to 70 % of all sporadic colorectal carcinomas, is characterised by a chromosomal instability (CIN) with the classical adenoma-carcinoma sequence due to alteration of the APC-betacatenin pathway with p53 mutations, SMAD alterations and LOH (loss of heterozygositiy) of 5q, 17 p 18q. On the other, the CpG island methylator phenotype (CIMP+) was described with an epigenetic inactivation of tumour suppressor genes that are typically inactivated by germline mutations in familiar cancer syndromes, e. g., Rb, VHL, hMLH1, p16 or BRCA. Colorectal carcinomas of the CIMP+ type often show a high microsatellite instability (MSI+) caused by aberrant promoter methylation of the missmatch repair gene hMLH1. Further CIMP+ are located in the proximal right-side colon and show a poor grading with mucinous or signet-cell differentiation.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Colorectal Neoplasms / epidemiology*
  • Colorectal Neoplasms / genetics*
  • Epigenesis, Genetic / genetics*
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Mutation / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Precancerous Conditions / epidemiology*
  • Precancerous Conditions / genetics*
  • Prevalence