Screening for genomic rearrangements of the MMR genes must be included in the routine diagnosis of HNPCC.

I n hereditary non-polyposis colorectal cancer (HNPCC), the most common form of inherited colorectal cancer, detection of the causal alteration of the mismatch repair (MMR) gene involved is essential for proper management of the families. This will allow the identification of relatives with high risk for colorectal or endometrial cancer, who require the appropriate screening and, conversely, will avert useless surveillance in non-carrier relatives. Mutational studies, based on conventional screening methods, have indicated that point mutations of MSH2, MLH1, or MSH6 can be detected in approximately 55% of the families, fulfilling the Amsterdam (AMS) criteria. These stipulate: