In 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,¹ 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:

• at least three relatives with colorectal cancer, or cancer of the endometrium, small bowel, ureter, or renal pelvis

• one of whom is a first degree relative of the other two

• at least two successive generations affected

• and at least one cancer diagnosed before the age of 50 years.²

In a recent study, we showed that genomic rearrangements of MSH2 are involved in approximately 20% of the AMS+ HNPCC families without detectable point mutations within MSH2 or MLH1.³ This study was performed using quantitative multiplex PCR of short fluorescent fragments (QMPSF), which can easily detect heterozygous genomic deletions and duplications.^3–7 This method is based on the simultaneous amplification of short genomic sequences under quantitative conditions, using dye labelled primers, and the superimposition of the electropherograms of patients and controls.