Somatic mutation rate of the APC gene

Abstract

Background: Somatic inactivation of the wild-type APC gene is involved in the development of adenoma of familial adenomatous polyposis. This situation is also true in sporadic adenomas. It is of biological interest to know the somatic mutation rate of the APC gene. Methods: The number of stem cells of the colon (N) and somatic mutation rate of the APC gene in a stem cell in a year (m) can induce age-specific incidence of adenomas. The number of stem cells was estimated as 108 according to previous reports. In the general population, expected adenomas at the end of age n years will be ~Nm2n2/4. In patients with polyposis, the expected number of adenomas will be Nmn/2. By setting several figures for m, the expected incidence of adenomas was compared with the actual occurrences. Results: If the mutation rate was set between 2/106 and 3/106 mutations/stem cell/year, the calculated numbers were well fitted to the actual data. Expected adenomas in polyposis patients at the age of 20 and 40 years were 2000 and 4000 and these were within actual experiences. Conclusions: This is the first study to estimate the somatic mutation rate of the APC gene. The estimated somatic mutation rate of the APC gene was between 2/106 and 3/106 mutations/stem cell/year.