LACK OF PMS2 GENE-TRUNCATING MUTATIONS IN PATIENTS WITH HEREDITARY COLORECTAL-CANCER

Hereditary non-polyposis colorectal cancer (HNPCC) is a genetically he terogeneous disease for which PMS2 gene, a member of the human PMS gen e family, is believed to have a marginal role. To better define the co ntribution of PMS2 to hereditary colorectal cancer, we investigated th is gene in 22 unrelated Italian patients that, despite a positive fami ly history and/or early onset and development of tumors with microsate llite instability (MSI), did not carry constitutional mutations of MLH 1 and MSH2 genes. No mutations with clear-cut pathogenetic significanc e were detected in the coding regions of PMS2 gene, but only 8 polymor phisms (7 common and 1 rare, 3 silent and 5 missense) and 3 unique mol ecular variants (2 missense substitutions and one 3-nucleotide deletio n) were seen. Lack of PMS2 truncating mutations in our study does not disagree with its supposed marginal involvement in hereditary colorect al cancer, but at the same time points out the need to investigate the phenotypic molecular and clinical characteristics more specifically a ssociated with PMS2 mutations.