Fig. 6

Combination spectrum of impactful somatic mutations in PIK3CA and PIK3R1 in breast cancer. a A mutually exclusive pattern of proliferation-associated mutations in PIK3CA and PIK3R1 was illustrated in breast cancer by functional screening. Left, somatic mutation frequencies and combined spectrum of PIK3CA and PIK3R1 mutations in the FUSCC cohort; right, proliferation-driver mutation frequencies and the combined spectrum of proliferation-driver mutations after screening. b Prevalence of proliferation-driver mutations in individual cancers: PIK3CA-driver mut (blue); PIK3R1-driver mut (red); PIK3CAor PIK3R1 non-driver mut (gray); no mutation (empty). c, e, g Growth properties of MCF-10A cells expressing a variety of combined PIK3CA and PIK3R1 mutations. Five wells were measured per condition. The error bars indicate ± s.d. derived from three independent experiments. d, f, h The levels of p-AKT at Ser-473 in the indicated cells were analyzed by western blotting. Western blots were representative of three independent experiments. i Hypothetical schematic model of dual impactful mutations of PIK3CA and PIK3R1 that regulate the PI3K pathway