Molecular basis of HNPCC: Mutations of MMR genes

Nickolas Papadopoulos, Annika Lindblom

Research output: Contribution to journalArticlepeer-review

149 Scopus citations


Hereditary nonpolyposis colorectal cancer (HNPCC) is inherited as a dominant disorder caused by germline defects in one of at least four mismatch repair (MMR) genes. Two of these genes, hMSH2 and hMLH1, account for the vast majority of the germline mutations in HNPCC kindreds, whereas hPMS1 and hPMS2 are mutated in only few families. MMR genes also are susceptible to somatic mutations in sporadic tumors. The mutational spectrum of the MMR genes shows no predominant type of mutation. Furthermore, the mutations are spread throughout the length of the genes, with no significant hot spots. Identification of MMR genes as the cause of HNPCC made presymptomatic diagnosis a reality. However, the presence of multiple genes and the heterogeneity of mutations present challenges to the development of diagnostic tests for this disease.

Original languageEnglish (US)
Pages (from-to)89-99
Number of pages11
JournalHuman mutation
Issue number2
StatePublished - Aug 19 1997


  • Germline mutation
  • Hereditary nonpolyposis colon cancer (HNPCC)
  • Mismatch repair (MMR)
  • Replication error (RER)
  • Somatic mutation
  • hMSH2, hMLH1, hPMS1, hPMS2, GTBP, hMSH3 genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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