Rapid Communication

Human Genetics

, Volume 97, Issue 2, pp 251-255

First online:

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

  • Yuri K. MaliakaAffiliated withDepartment of Medical Genetics, Sechenov Moscow Medical Academy
  • , Alla P. ChudinaAffiliated withLaboratory of Prevention of Carcinogenic Actions, Cancer Research Center, RAMS
  • , Nicodim F. BelevAffiliated withDepartment of Oncogenetics, Institute of Oncology of Moldavia
  • , Pablo AldayAffiliated withBasel Institute for Immunology
  • , Nikolay P. BochkovAffiliated withDepartment of Medical Genetics, Sechenov Moscow Medical Academy
  • , Jean-Marie BuersteddeAffiliated withBasel Institute for Immunology

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access


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 hMLHI. 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.