Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant predisposition for early-onset colorectal cancer and associated tumour types caused by mutations in DNA mismatch repair genes, mainly MLH1 and MSH2. The Amsterdam criteria, stressing familial tumour events, as well as the less stringent Bethesda criteria, help to raise suspicion of HNPCC.
Mutation screening in a colon cancer patient of young age but negative family history revealed the MSH2 splice site mutation c.2006-2A>G. This mutation was present in all three germ cell layers in the patient, but absent in her biological parents, reporting the second case of de-novo germline mutation in MSH2.
Our findings suggest that at least in approximately 1% of mutation-positive cases, a de-novo event might be involved. The identification of a newly evolved rare mutation calls for alertness and encourages the application of the Bethesda guidelines and certain clinical and histopathological features to define candidates for HNPCC gene mutation screening despite a negative family history.