LAUSR

Double mutations in an oncogene enhance tumor growth Cancer is predominantly a genetic disease. Numerous gain-of-function mutations and gene amplifications that promote cell growth and survival have been identified in human cancer genomes through the efforts of large-scale sequencing projects. One of the most frequently mutated oncogenes in all human cancers is PIK3CA [phosphatidylinositol 4,5-bisphosphate (PIP2) 3-kinase catalytic subunit α], which encodes the catalytic subunit (p110α) of phosphoinositide 3-kinase (PI3K) (1). Oncogenic mutations in PIK3CA hyperactivate downstream signaling and promote phenotypes associated with malignancy. On page 714 of this issue, Vasan et al. (2) find that double mutations (two different mutations in one allele) in PIK3CA occur with much higher frequency in cancer genomes, particularly breast cancers, than previously thought. Double mutations result in increased PI3K pathway activity and tumor growth and predict increased sensitivity of human breast cancer to PI3K inhibitors.