TP53 and cancer: Genome sequencing analyses of lifestyle cancers have confirmed that the usual genetic stigmata of tumorigenic transformation comprise a small group of aberrations (43–46), consistent with the model of tumor suppressor gene loss proposed above: namely, anti-apoptotic dysfunctions affecting either TP53 (including those secondary to BRCA mutations (47) or PTEN; gain-of-function mutations affecting KRAS or PIK3CA; or MSI (flagged by low MMR expression on histochemistry) with or without activating BRAF mutations (48).