Mutational analysis of mismatch repair genes, hMLH1 and hMSH2, in sporadic endometrial carcinomas with microsatellite instability

Jpn J Cancer Res. 1996 Feb;87(2):141-5. doi: 10.1111/j.1349-7006.1996.tb03151.x.


Microsatellite instability, monitored by replication error (RER), has been observed in both sporadic and hereditary types of endometrial carcinoma. In the hereditary tumors, this instability is considered to be caused by a germline defect in the DNA mismatch-repair system. We previously reported that nearly one-quarter of sporadic endometrial carcinomas examined revealed an RER-positive phenotype at multiple microsatellite loci. To investigate the role of genetic alterations of DNA mismatch-repair genes in sporadic endometrial carcinomas, we screened 18 RER(+) endometrial carcinomas for mutations of hMLH1 and hMSH2. Although we found no germline mutations, we detected two somatic mutations of hMLH1 in a single endometrial cancer; these two mutations had occurred on different alleles, suggesting that two separate mutational events had affected both copies of hMLH1 in this particular tumor. These data implied that mutations of hMLH1 or hMSH2 play limited roles in the development of sporadic endometrial carcinomas, and that the tumors with genetic instability might have alterations of other mismatch-repair genes, such as hPMS1 and hPMS2, or of unknown genes related to the mismatch-repair system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Base Sequence
  • Carcinoma / genetics*
  • Carrier Proteins
  • DNA Mutational Analysis
  • DNA Primers / chemistry
  • DNA Repair*
  • DNA-Binding Proteins*
  • Endometrial Neoplasms / genetics*
  • Exons
  • Female
  • Humans
  • Microsatellite Repeats
  • Molecular Sequence Data
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Neoplasm Proteins / genetics*
  • Nuclear Proteins
  • Polymorphism, Single-Stranded Conformational
  • 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
  • MSH2 protein, human
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein