In vivo multiplexed interrogation of amplified genes identifies GAB2 as an ovarian cancer oncogene.

High-grade serous ovarian cancers are characterized by widespread gain and loss of copy number involving large numbers of genes; however, the functional consequences of many of these changes remain unclear. To determine which of the many amplified genes exhibited tumor-promoting behavior, we developed a novel in vivo method to systematically screen potential oncogenes for tumor formation. We identified GAB2, a signaling adaptor protein, as a potent oncogene that is also significantly amplified in ovarian and breast cancer. GAB2 overexpression activates the phosphatidylinositol 3-kinase (PI3K) pathway and confers sensitivity to PI3K pathway inhibition. These results credential GAB2 as a potent oncogene in ovarian cancer and emphasize the importance of PI3K signaling in this cancer.