Low prevalence of germline hMSH6 mutations in colorectal cancer families from Spain

World J Gastroenterol. 2005 Oct 7;11(37):5770-6. doi: 10.3748/wjg.v11.i37.5770.


Aim: To investigate the prevalence and penetrance of hMSH6 mutations in Spanish HNPCC families that was negative for mutation in hMLH1 or hMSH2.

Methods: We used PCR-based DGGE assay and direct sequencing to screen for hMSH6 gene in 91 HNPCC families.

Results: we have identified 10 families with germ-line mutations in the DNA sequence. These mutations included two intronic variation, three missense mutation, one nonsense mutation, and four silent mutations. Among the 10 germ-line mutations identified in the Spanish cohort, 8 were novel, perhaps, suggesting different mutational spectra in the Spanish population. Detailed pedigrees were constructed for the three families with a possible pathogenic hMSH6 mutation. The two silent mutations H388H and L758L, detected in a person affected of colorectal cancer at age 29, produce loss of the wild-type allele in the tumor sample. Immunohistochemical analysis showed that expression of MSH6 protein was lost only in the tumors from the carriers of V878A and Q263X mutations.

Conclusion: Altogether, our results indicate that disease-causing germ-line mutations of hMSH6 are very less frequent in Spanish HNPCC families.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pair Mismatch
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • DNA Mutational Analysis
  • DNA Repair
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Female
  • Genetic Testing*
  • Humans
  • Male
  • Mutation*
  • Pedigree
  • Spain


  • DNA-Binding Proteins
  • G-T mismatch-binding protein