Uncertainties In Tumor Allele Frequencies Limit Power To Infer Evolutionary Pressures

We read with great interest the paper by Williams, et. al.[1], who argued for neutral evolution in tumors by analyzing The Cancer Genome Atlas (TCGA) data. They supported this conclusion by showing high R2 values for fits to a neutral evolution model predicting M {propto} 1 / f, where M is the number of somatic mutations with allele frequency [≥] f. However, we believe a conclusion of neutrality must be treated cautiously, as high R2 values are consistent with many evolutionary models.