An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer.

摘要: Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in cancer. By applying mass spectroscopy-based sequencing and reverse-phase protein arrays to 547 human breast cancers 41 cell lines, we determined the subtype specificity signaling effects of PIK3CA, AKT, PTEN mutations PIK3CA on responsiveness PI3K inhibition vitro outcome after adjuvant tamoxifen. were more hormone receptor-positive (34.5%) HER2-positive (22.7%) than basal-like tumors (8.3%). AKT1 (1.4%) (2.3%) restricted cancers. Unlike that absent from (39%) (20%) lines tumors, suggesting a selection for these but not during adaptation culture. did have significant effect tamoxifen therapy 157 cancer patients. mutations, comparison with loss associated significantly less inconsistent activation AKT downstream PI3K/AKT lines. mutation frequently concordant, different contributions pathophysiology. rendered cells sensitive growth by inhibitor LY294002 mutations. Thus, likely play distinct role pathogenesis subtypes. The specific aberration present may implications PI3K-targeted therapies