Mutations in MLH1 are more frequent than in MSH2 in sporadic colorectal cancers with microsatellite instability

Genes Chromosomes Cancer. 1997 Jan;18(1):42-9. doi: 10.1002/(sici)1098-2264(199701)18:1<42::aid-gcc5>;2-1.


The microsatellite instability that is a feature of tumors in patients with hereditary nonpolyposis colorectal cancer (HNPCC) is a consequence of defective DNA mismatch repair. Mutations in the DNA mismatch repair genes MSH2 and MLH1 may account for up to 90% of HNPCC kindreds. Microsatellite instability is also seen in 10-16% of sporadic colorectal cancers. A limited number of MSH2 and MLH1 mutations have been described for sporadic colorectal cancers. In this study, we screened 12 primary sporadic colorectal cancers with microsatellite instability for mutations in MSH2 and MLH1 by using reverse transcription-polymerase chain reaction (RT-PCR) and single-strand-conformation-variant (SSCV) analysis. Eight mutations were identified in six tumors. One mutation in MLH1 was found to be present in the patient's germline DNA. Four tumors had somatic mutations in MLH1, and, in two of these tumors, two different mutations were identified. A single tumor had a somatic MSH2 mutation. Our observations suggest that MLH1 is mutated more frequently than MSH2 in sporadic colorectal cancers with microsatellite instability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Southern
  • Carrier Proteins
  • Colorectal Neoplasms / genetics*
  • DNA Mutational Analysis
  • DNA Repair / genetics*
  • DNA, Neoplasm / analysis
  • DNA-Binding Proteins*
  • Gene Amplification
  • Humans
  • Microsatellite Repeats
  • Middle Aged
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Mutation* / genetics
  • Neoplasm Proteins / genetics*
  • Nuclear Proteins
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Polymorphism, Single-Stranded Conformational
  • Proto-Oncogene Proteins / genetics*
  • RNA, Neoplasm / analysis
  • RNA-Directed DNA Polymerase
  • Sequence Analysis, DNA


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