A new interphase fluorescence in situ hybridization approach for genomic rearrangements involving MLH1 and MSH6 in hereditary nonpolyposis colorectal cancer-suspected mutation-negative patients.

摘要

Hereditary nonpolyposis colorectal cancer (HNPCC; Lynch syndrome) is the most frequent autosomal dominant predisposition for colorectal cancer and is found in 2-5% of all patients [1-3]. On the molecular level, HNPCC is characterized by microsatellite instability [4-6] based on germline mutations in one of the mismatch repair (MMR) genes, mostly MLH1 or MSH2, less frequently MSH6 or PMS2. The causes of HNPCC are heterogeneous. Mutations of the MLH1, MSH2, or MSH6 genes are identified in 70-80% of all cases including unclassified variants [7-9], and larger deletions in the MLH1 or the MSH2 genes are found in another 10% of cases [10,11].