The phosphatidylinositol 3 '-kinase p85 alpha gene is an oncogene in humanovarian and colon tumors

Phosphatidylinositol 3'-kinases (PI3ks) are a family of lipid kinases that play a crucial role in a wide range of important cellular processes associa ted with malignant behavior including cell growth, migration, and survival. We have used single-strand conformational polymorphism/heteroduplex analys is to demonstrate the presence of somatic mutations in the gene for the p85 alpha regulatory subunit of PI3k (PIK3R1) in primary human colon and ovari an tumors and cancer cell lines. All of the mutations lead to deletions in the inter-SH2 region of the molecule proximal to the serine(608) autoregula tory site. Expression of a mutant protein with a 23 amino acid deletion lea ds to constitutive activation of PI3k providing the first direct evidence t hat p85 alpha is a new oncogene involved in human tumorigenesis.