Our analyses show that (a) each cell of a relatively small human tumor of 1 cm3 harbors approximately 900 individual mutations, assuming a spontaneous mutation rate of 5×10−9/bp/cell cycle.
We allow for variation of the selective effects of arising mutations, assuming a Gamma distribution, with shape and scale parameters, α and β, respectively, implying a mean E(S) = αβ.
In case that the ancestral allele codes stop codon, we do not regard this SNP as nonsense SNP, but is a read-through mutation assuming that there was a variant having a shorter ORF.
Using outgroup information to polarize mutations and assuming an infinite-sites mutation model, polymorphic sites in a nonrecombining alignment can be summarized as counts of mutations on each possible genealogical branch without loss of information.
One mutation assumed to increase a woman's risk of breast cancer was shown to instead increase the likelihood of ovarian cancer, while other mutations thought to increase the risk of breast cancer seemed instead to have little effect.
After testing for the mutation rate, the comparison of topologies assuming a particular mutation rate distribution allows us to check for which topology presents a higher posterior probability.
Thus, we get an expected value of 3450 experimentally detectable mutations per cell in a tumor of about 1 cm3 or ∼109 cells, assuming a mutation rate of 5×10−9/bp/cell cycle and a modest death rate.
Tomlinson et al. [6] have estimated 1250 mutations per adenocarcinoma cell (in a cancer that has grown over 1000 cell cycles), assuming a mutation rate of 5×10−9 per bp per cell cycle.
This could occur once every 46 million years, assuming a mutation rate of one nucleotide every 95,000 years and 2,085 generations per year (S.
Assuming a mutation rate of 1.5×10−8 per year [50] and a generation time of 2 years, parameter estimates of the model can be converted into estimates of effective population size (Ne) and time in years (Table 1).
