An update on Lynch syndrome

Recent advances in hereditary nonpolyposis colorectal cancer (HNPCC) have been made based on the discovery early in this decade that germline mutations in genes responsible for repair of DNA mismatches formed the molecular basis for the syndrome. Several studies during the past year described the prevalence of germline mutations in those deemed at risk for HNPCC and helped define who should be tested for such mutations. Investigators are also beginning to make connections between genotype and phenotype; it appears that certain mutations are more likely than others to generate a broad spectrum of extracolonic tumors. Carcinogenetic mechanisms in HNPCC also received attention; evidence continues to accumulate that the critical somatic mutations driving malignant transformation in HNPCC (and in sporadic colorectal cancer with microsatellite instability) are different from the critical mutations seen in most colon cancers. Finally, several contributions dealt with the complicated question of how to manage germline carriers and affected individuals.