Microsatellite instability in colorectal-cancer patients with suspected genetic predisposition

Int J Cancer. 2000 Jan 20;89(1):87-91. doi: 10.1002/(sici)1097-0215(20000120)89:1<87::aid-ijc14>3.0.co;2-9.


Hereditary non-polyposis colorectal cancer (HNPCC) is a dominantly inherited syndrome linked to DNA-mismatch-repair (MMR) gene defects, which also account for microsatellite instability (MSI) in tumour tissues. Diagnosis is based mainly on family history, according to widely accepted criteria (Amsterdam Criteria: AC). Aim of this work was to assess MSI in colorectal-cancer patients with suspected genetic predisposition, and to verify whether MSI represents a tool to manage MMR gene (hMSH2 and hMLH1) mutation analysis. We investigated 13 microsatellites (including the 5 NCI/ICG-HNPCC markers) in 45 patients with suspected hereditary predisposition (including 16 subjects from HNPCC families fulfilling the AC). We found MSI-H (high frequency of instability, i.e., in > or =30% of the markers) in 85% of the HNPCC patients and in 16% of the non-HNPCC subjects. The 5 NCI/ICG-HNPCC microsatellites proved to be the most effective in detecting MSI, being mononucleotide repeats the most unstable markers. We investigated the association between hMSH2- and hMLH1 gene mutations and MSI. Our results indicate that AC are highly predictive both of tumour instability and of MMR-gene mutations. Therefore, as the most likely mutation carriers, HNPCC subjects might be directly analyzed for gene mutations, while to test for MSI in selected non-HNPCC patients and to further investigate MMR genes in MSI-H cases, appears to be a cost-effective way to identify subjects, other than those from kindred fulfilling AC, who might benefit from genetic testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Pair Mismatch*
  • Child
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • DNA Repair*
  • DNA, Neoplasm / analysis
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Microsatellite Repeats*
  • Mutation*


  • DNA, Neoplasm