hMSH2 is the most commonly mutated MMR gene in a cohort of Greek HNPCC patients

Br J Cancer. 2005 Jan 31;92(2):396-404. doi: 10.1038/sj.bjc.6602260.


Germline mutations in genes encoding proteins involved in DNA mismatch repair are responsible for the autosomal dominantly inherited cancer predisposition syndrome hereditary nonpolyposis colorectal cancer (HNPCC). We describe here analysis of hMLH1 and hMSH2 in nine Greek families referred to our centre for HNPCC. A unique disease-causing mutation has been identified in seven out of nine (78%) families. The types of mutations identified are nonsense (five out of seven) (hMLH1: E557X, R226X; hMSH2: Q158X, R359X and R711X), a 2 bp deletion (hMSH2 1704_1705delAG) and a 2.2 kb Alu-mediated deletion encompassing exon 3 of the hMSH2 gene. The majority of mutations identified in this cohort are found in hMSH2 (77.7%). Furthermore, four of the mutations identified are novel. Finally, a number of novel benign variations were observed in both genes. This is the first report of HNPCC analysis in the Greek population, further underscoring the differences observed in the various geographic populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Base Sequence
  • Carrier Proteins
  • Chromatography, High Pressure Liquid
  • Colorectal Neoplasms, Hereditary Nonpolyposis / epidemiology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Greece
  • Humans
  • Male
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Mutation
  • Neoplasm Proteins / genetics
  • Nuclear Proteins
  • Pedigree
  • Proto-Oncogene Proteins / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction


  • 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