Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1 mutations

Clin Genet. 2004 Mar;65(3):215-25. doi: 10.1111/j.1399-0004.2004.00214.x.


Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant, inherited condition that is characterized primarily by the development of early-onset colorectal cancer and a number of other epithelial malignancies. The underlying genetic basis of the disease is associated with a breakdown of DNA-mismatch repair. There are many genes involved in DNA-mismatch repair, and five of them have been implicated in HNPCC. Two of the genes (hMSH2 and hMLH1) account for the majority of HNPCC families (approximately 60%), and it is not known what the exact contributions of the remaining three genes (hPMS1, hPMS2, and hMSH6) are in relation to this condition. In addition, a sixth gene (hEXO1) has been associated with a disease phenotype that is consistent with HNPCC. Current estimates suggest that all four of these genes, combined, may account for up to 5% of families. In this report, we examine the contribution of hPMS2 and hEXO1 to a well-defined set of families that fulfill the diagnostic criteria for HNPCC. The genes, hPMS2 and hEXO1, were studied by denaturing high performance liquid chromatography (DHPLC) analysis in 21 families that have previously been determined not to have mutations in hMSH2 or hMLH1. hPMS2 accounts for a small proportion of HNPCC families, and none were deemed to be associated with hEXO1. Mutations in hPMS2 appear to account for a small proportion of families adhering to the Amsterdam II criteria, whereas hEXO1 does not appear to be associated with HNPCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adenosine Triphosphatases / genetics*
  • Adult
  • Aged
  • Carrier Proteins
  • Chromatography, High Pressure Liquid
  • Colorectal Neoplasms, Hereditary Nonpolyposis / epidemiology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • DNA Mutational Analysis
  • DNA Primers
  • DNA Repair / genetics
  • DNA Repair Enzymes / genetics*
  • DNA-Binding Proteins / genetics*
  • Exodeoxyribonucleases / genetics*
  • Family Health
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2
  • Molecular Epidemiology
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Mutation / physiology*
  • Neoplasm Proteins / genetics
  • Nuclear Proteins
  • Proto-Oncogene Proteins / genetics


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA Primers
  • DNA-Binding Proteins
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • EXO1 protein, human
  • Exodeoxyribonucleases
  • Adenosine Triphosphatases
  • PMS2 protein, human
  • MSH2 protein, human
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • DNA Repair Enzymes