Mismatch repair gene mutations and cancer risks: an update

De novo mutations Carriers of a germline mutation in a DNA mismatch repair (MMR) gene, i.e. persons with Lynch syndrome, have substantially high risks of colorectal, endometrial, and several other cancers. The proportion of carriers who have de novo mutations (not inherited from either parent) is not known. Of 261 probands (202 clinicbased, 59 population-based) with MMR gene mutations for whom it was possible to determine the origin of the mutation, six (2.3%, 95%CI = 0.9–5.0%) were confirmed as de novo and the remaining 255 (97.7%, 95%CI = 95.0–99.1%) were inherited. Of the de novo mutation carriers, three were clinic-based probands (1.5%, 95%CI = 0.3–4.5%) and three were population-based probands (5.1%, 95%CI = 1.2–14.5%). Two were in MLH1, three in MSH2, and one in MSH6. These mutation carriers were recruited from family cancer clinics in Perth and Brisbane and via the Victorian Cancer Registry, Australia, and from Mayo clinic and via the Minnesota Cancer Surveillance System, USA. De novo MMR gene mutations are uncommon causes of Lynch syndrome.