Functional characterization of a novel somatic oncogenic mutation of .

Class I phosphoinositide 3-kinase (PI3K) enzymes have attracted considerable attention as drug targets in cancer therapy over the last 20 years. The signaling pathway triggered by class I PI3Ks is dysregulated in a range of tumor types, impacting cell proliferation, survival and apoptosis. Frequent oncogenic mutations of have previously been discovered. In contrast, reports of mutations have been limited; however, in most cases, those that have been identified have been shown to be activating and oncogenic. The functional characterization of a catalytic domain mutant, p110β, first discovered by others in castrate-resistant prostate cancer (mCRPC), is outlined in this report; our data suggest that p110β is a gain-of-function mutation, driving PI3K signaling, tumorigenic cell growth and migration. Tumor cells expressing p110β are sensitive to p110β inhibition; its characterization as an oncogenic driver adds to the rationale for targeting p110β and indicates a continuing need to further develop specific PI3K inhibitors for clinical development in cancer therapy.