Colon cancer and DNA repair: have mismatches met their match?

Abstract

Recently, both a common inherited human cancer, hereditary non-polyposis colorectal carcinoma (HNPCC), and certain sporadic human cancers have been shown to have frequent alterations in microsatellite sequences. These were ascribed to a defect in the correction of errors of replication; indeed, the cell line H6, which is derived from an HNPCC tumour, has been shown to be deficient in mismatch repair. The HNPCC locus on chromosome 2p has been linked to a gene hMSH2, which encodes a 100 kDa mismatch-binding protein that has an extensive degree of sequence conservation from bacteria through yeast to humans. But could a malfunction of this protein alone cause cancer?