GENOMIC LOCI SUSCEPTIBLE TO REPLICATION ERRORS IN CANCER-CELLS

Microsatellite instability due to a deficiency in DNA mismatch repair is characteristic of a replication error (RER) phenotype. This widespr ead genomic instability is well documented in hereditary non-polyposis colon cancer (HNPCC) as well as subsets of sporadic carcinomas. Featu res of the RER phenotype such as the early appearance in tumour develo pment and better prognosis of RER+ colorectal tumours render its exami nation important for cancer patients. Recently, we identified four loc i that were shown to be highly susceptible to RER in cancer cells. Her e, we used these loci to detect the RER phenotype in sporadic carcinom as of colon, breast, lung, endometrium and ovary. Replication errors r evealed by these four markers followed the same tumour specificity as observed in HNPCC patients. In particular, 24% (6/25) of colorectal, 3 3% (4/12) of endometrial and 17% (2/12) of ovarian cancers displayed t he RER phenotype characterized by an increased allelic mobility, where as none of the breast (n = 22) and the lung (n = 27) carcinomas were f ound to be unstable. Assaying RERs sensitive loci provides us with a u seful diagnostic tool for HNPCC-like sporadic tumours.