Reconstruction of a hierarchical timeline of mutations showed that the earliest mutations relate to a small subset of recurrent drivers, including TP53 gene – often enabled by early loss of chromosome 17 petite arm, telomerase gene TERT, CDKN2A, and KRAS. The small number of initial changes in cancer evolution suggests an epistatic fitness landscape constraining those first steps in cancer evolution. This evidence concerns the gene TERT and cancer.