Analysis of mutations in TP53, APC, K-ras, and DCC genes in the non-dysplastic mucosa of patients with inflammatory bowel disease

Int J Colorectal Dis. 2009 Oct;24(10):1141-8. doi: 10.1007/s00384-009-0748-5. Epub 2009 Jun 20.

Abstract

Background and aims: Patients with ulcerative colitis (UC) and Crohn's disease (CD) have a high risk for colorectal cancer (CRC). To understand the molecular basis of colitis-associated CRC, we analyzed alterations in TP53, APC, K-ras, and DCC genes in the non-dysplastic UC and CD colon.

Materials and methods: Endoscopic biopsies were collected from six predefined colon sites of 35 UC and 12 CD patients for DNA extraction and genetic analysis.

Results: A mutation was found in codon 1141 of the APC gene of two CD patients, being somatic in one and germinative in the other. The mutation seen in both patients was a base exchange of thymine for cytosine, resulting in an exchange of leucine for serine. We did not detect any mutations in the other samples analyzed.

Conclusions: Mutations in APC gene may occur in the non-dysplastic CD mucosa of patients with disease for more than 10 years. The follow-up of these patients will show the likelihood of mutant APC progressing to CRC in CD. Further analysis will be required for evaluating the impact of these findings in the context of cancer surveillance in inflammatory bowel disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics*
  • Adolescent
  • Adult
  • Aged
  • Base Sequence
  • Codon / genetics
  • Colitis, Ulcerative / genetics
  • Colitis, Ulcerative / pathology
  • Crohn Disease / genetics
  • Crohn Disease / pathology
  • DCC Receptor
  • DNA Mutational Analysis
  • Female
  • Humans
  • Inflammatory Bowel Diseases / genetics*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation / genetics*
  • Point Mutation / genetics
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Receptors, Cell Surface / genetics*
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Young Adult
  • ras Proteins / genetics*

Substances

  • Adenomatous Polyposis Coli Protein
  • Codon
  • DCC Receptor
  • DCC protein, human
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Receptors, Cell Surface
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins