Uncertainties in tumor allele frequencies limit power to infer evolutionary pressures.

Abstract

Williams, et. al. (Nature Genetics 48:238, 2016) have argued for neutral evolution in tumors by analyzing The Cancer Genome Atlas data. They supported this conclusion by showing high R^2 values for fits to a neutral evolution model predicting M∝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 we show that high R^2 values are consistent with many evolutionary models.