Our observation that, with the possible exception of the PI3K-FOXO pathway, the variation in pathway activity was generally not larger at the macro-scale than micro-scale, and for the HH and TGFβ pathways, even higher at the micro-scale, is compatible with currently emerging ideas on a Big Bang type of cancer evolution based on genomic analysis of PT, in which macro-scale heterogeneity appeared to be not the dominant form [17]. The gene discussed is TGFB1; the disease is cancer.