Abstract 5502: Characterization of a hotspot PTEN mutation in endometrial cancer

Endometrial cancer is the most common gynecologic malignancy in the developed world. These cancers harbor the highest rates of PI3K pathway alterations reported, with PTEN being the most frequently altered gene. Differently from other cancer types, in endometrial cancer a specific hotspot mutation in the lipid phosphatase domain of PTEN is present at residue 130. This hotspot mutation significantly co-occurs with other mutations in the PI3K pathway, such as PIK3CA and PIK3R1. Interestingly, in the TCGA data we also found a positive correlation between this mutation and the expression level of the estrogen receptor alpha. Although it has been reported that the PTEN-R130 mutant loses its lipid phosphatase activity in vitro, little is known regarding the other unconventional functions of PTEN, such as its protein phosphatase activity. We performed unbiased phospho-proteomics experiments in order to explore the impact of this specific mutation in multiple endometrial cancer cell models. Citation Format: Ye Wang, Charles Jakubik, Rachel Peterson, Cyril Benes, Wilhelm Haas, Jeffrey Engelman, Carlotta Costa. Characterization of a hotspot PTEN mutation in endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5502.