| Comments |
P.1484 left column bottom paragraph: "Based on a Poisson probability distribution in which mutations are independent events, the average stem cell would accumulate 1 to 2 mutations. As many as 2×10^6 cells could contain as many as 6 mutations, and a few cells (3) could contain as many as 12 mutations (Table 1). If each of the cells with multiple mutations were able to proliferate continuously and form a tumor, then spontaneous mutation rates could account for the 6 to 10 events (mutations) that are predicted to be rate-limiting for tumor formation, based on the increase of cancer incidence with age (Armitage and Doll 1954). In this analysis [investigators] assume that any mutation in any gene is on the pathway toward malignancy, that any stem cell has the potential to become a tumor, and that each of the mutations are rate-limiting for the development of a malignancy. If [they] restrict the analysis to mutations in cancer-associated genes, then the spontaneous mutation rate can account for as many as 8×10^3 stem cells containing as many as 2 mutations, and only a few cells (5) containing as many as 3 mutations." |