Somatic Mutations in Normal Tissues: New Perspectives on Early Carcinogenesis

Normal tissues progressively acquire mutations. Some mutations are positively selected, driving clonal expansions that may colonize the majority of a tissue by old age. In several cases mutant expansion is due to biasing stem cell fate toward proliferation. However, expansionary phase transient and followed reversion wild-type behavior so normal integrity retained. Here we consider implications these findings for carcinogenesis. We propose be considered cancer driver, gene should more prevalent in tumors than lineage from which it emerged. Cancer risk not dependent on mutational burden, but rather reflect relative frequency pro- anti-oncogenic mutants within tissue. Understanding basis advantage over cells allows interventions halt or even deplete oncogenic tissue, potentially lowering risk.