Mutational analysis of MLH1 and MSH2 in 25 prospectively-acquired RER+ endometrial cancers

Genes Chromosomes Cancer. 1997 Mar;18(3):219-27. doi: 10.1002/(sici)1098-2264(199703)18:3<219::aid-gcc8>;2-4.


Mutations in the DNA mismatch repair (MMR) genes MLH1 and MSH2 have been linked to several human cancers which display the replication error (RER) phenotype. Germline mutations in these two genes have been implicated in about 90% of families with hereditary nonpolyposis colorectal cancer (HNPCC). A significant proportion of endometrial cancers, the second most common malignancy of the HNPCC syndrome, also exhibit RER. We screened 125 primary endometrial adenocarcinomas with seven microsatellite markers and identified 25 specimens with RER (20%). We used single-strand conformation variant analysis to search for mutations in MLH1 and MSH2. Direct sequencing of variants revealed only one germline mutation in MLH1 and a single somatic mutation in MSH2. However, six previously unreported sequence polymorphisms in MLH1 were identified. Four of these polymorphisms show clear population-based differences in allele frequency. In addition, a highly informative marker for MLH1 was characterized. The low frequency of mutations in MLH1 and MSH2 in this large series of cancers suggests that other MMR genes are responsible for the RER phenotype in endometrial cancers.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Carrier Proteins
  • DNA Mutational Analysis
  • DNA Repair*
  • DNA Replication*
  • DNA, Neoplasm / analysis
  • DNA-Binding Proteins*
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Frequency
  • Genetic Markers
  • Humans
  • Middle Aged
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Nuclear Proteins
  • Polymorphism, Genetic*
  • Polymorphism, Single-Stranded Conformational
  • Proto-Oncogene Proteins / genetics*


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