Disease-causing gene-flanking genomic rearrangements in HNPCC patients

Background The molecular diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) or Lynch-Syndrome is the detection of a pathogenic germline mutation in one of the DNA mismatch repair (MMR) genes. However, in ~10-20% of cases suspected of Lynch-syndrome no disease-causing mechanism can be detected. Genomic rearrangements such as gene-flanking deletions, inversions, duplications, or translocations might affect MMR genes but are difficult to detect. We report here two different disease-causing rearrangement mechanisms in HNPCC patients flanking the gene in question.