PIK3CA and cancer: Oncogenic mutations universally result in an activated protein, but biological effects of different mutations in the same oncogene can result in disparate clinical phenotypes and have distinct therapeutic implications.33-36 Using matched GENIE cohorts, we examined the distribution of hotspot alterations at the mutation-level for the most commonly altered oncogenes including KRAS, PIK3CA, BRAF, and EGFR among cancer types where the oncogene of interest was frequently mutated.