Abstract IS02: BCAM-AKT2 FUSION GENE LEADS TO A CONSTITUTIVELY ACTIVATED AKT2 FUSION KINASE IN HGSC

Abstract

Abstract High-grade serous ovarian cancer (HGSC) is among the most lethal forms of cancer in women. Excessive genomic rearrangements, which are expected to create fusion oncogenes, are the hallmark of this cancer. Using high-throughput RNAseq, we identify a cancer-specific gene fusion between BCAM, a membrane adhesion molecule, and AKT2, a key kinase in the PI3K signaling pathway. This fusion is present in 7% of patient cancers tested, a significant frequency considering the highly heterogeneous nature of this malignancy. We provide direct evidence that BCAM-AKT2 is translated into an in-frame fusion protein in the patient's tumor. The resulting AKT2 fusion kinase is membrane-associated, constitutively phosphorylated, and activated as a functional kinase in cells, suggesting a new mechanism of AKT2 kinase activation in HGSC. This recurrent genomic alteration is a potential therapeutic target and marker of a clinically relevant subtype for tailored therapy of HGSC. Citation Format: Laising Yen. BCAM-AKT2 FUSION GENE LEADS TO A CONSTITUTIVELY ACTIVATED AKT2 FUSION KINASE IN HGSC [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr IS02.