CpG dinucleotides in the hMSH2 and hMLH1 genes are hotspots for HNPCC mutations

Hum Genet. 1996 Feb;97(2):251-5. doi: 10.1007/BF02265276.


Hereditary nonpolyposis colon cancer (HN-PCC) is an autosomally inherited predisposition to cancer that has recently been linked to defects in the human mismatch repair genes hMSH2 and hMLH1. The identification of the causative mutations in HNPCC families is desirable, since it confirms the diagnosis and allows the carrier status of unaffected relatives at risk to be determined. We report six different new mutations identified in the hMSH2 and hMLH1 genes of Russian and Moldavian HNPCC families. Three of these mutations occur in CpG dinucleotides and lead to a premature stop codon, a splicing defect or an amino-acid substitution in an evolutionary conserved residue. Analysis of a compilation of published mutations including our new data suggests that CpG dinucleotides within the coding regions of the hMSH2 and hMLH1 genes are hotspots for single base-pair substitutions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Base Sequence
  • Carrier Proteins
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • CpG Islands / genetics*
  • DNA-Binding Proteins*
  • Exons / genetics
  • Female
  • Humans
  • Male
  • Moldova
  • Molecular Sequence Data
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Nuclear Proteins
  • Pedigree
  • Proto-Oncogene Proteins / genetics*
  • Russia


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA-Binding Proteins
  • MLH1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein