Molecular genetics of hereditary non-polyposis colorectal cancer (HNPCC)

Alessandro Cama, Maurizio Genuardi, Ginevra Guanti, Paolo Radice, Liliana Varesco

Research output: Contribution to journalArticlepeer-review


The story of the molecular genetics of HNPCC is one of astonishingly rapid achievements. In just 16 months, from May 1993 to September 1994, four different genes, namely hMSH2, hMLH1, hPMS1 and hPMS2 have been identified and demonstrated to be associated with the disease. Their cloning was facilitated by the finding that tumor cells in HNPCC patients display a hypermutability of DNA short tandem repeats (microsatellite instability). In fact, HNPCC associated genes are the human counterparts of genetic elements known to control the fidelity of DNA replication in lower organisms. So far, more than 50 germline mutations of hMSH2 and hMLH1 genes have been reported in HNPCC kindreds. In addition, somatic mutations have been documented in hereditary as well as sporadic cancers. Unfortunately, the molecular diagnosis of HNPCC is hampered by the lack of mutational 'hot spots' and of clearly defined genotype-phenotype correlations and different screening methods are to be employed for the analysis of affected and at-risk individuals.

Original languageEnglish
Pages (from-to)122-135
Number of pages14
Issue number2
Publication statusPublished - Mar 1996


  • DNA mutations
  • DNA repair
  • genetic instability
  • molecular diagnosis

ASJC Scopus subject areas

  • Cancer Research


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