Abstract 1537: 3p13-14 FOXP1-SHQ1 deletion spanning multiple potential tumor suppressor genes cooperates with PTEN loss in cancer

Abstract

Abstract The recurrent 3p13-14 deletion spanning from FOXP1 to SHQ1 occurs frequently in prostate cancer and is broadly lost in a range of cancer types, but this deletion has unknown tumor suppressive potential. FOXP1-SHQ1 deletion significantly co-occurs with PTEN loss in prostate cancer and other cancers. We find that FOXP1-SHQ1 deletion cooperates with PTEN loss to accelerate prostate cancer development in mice, resulting in tumors with increased proliferation and highly anaplastic dedifferentiation. FOXP1-SHQ1 deletion in these PTEN null tumors results in selective mTORC1 pathway hyperactivation beyond that mediated by PTEN loss alone. FOXP1-SHQ1 deletion also partially rescues AR target gene inhibition caused by PTEN loss, circumventing the repression of the androgen axis seen upon PI3K pathway activation. Clinically, combined FOXP1 and PTEN loss is associated with increased prostate cancer recurrence, and this finding extends to other cancer types, most notably breast cancer. Citation Format: Haley Hieronymus, Philip J. Iaquinta, John Wongvipat, Anuradha Gopalan, Rajmohan Murali, Ninghui Mao, Brett S. Carver, Charles L. Sawyers. 3p13-14 FOXP1-SHQ1 deletion spanning multiple potential tumor suppressor genes cooperates with PTEN loss in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1537. doi:10.1158/1538-7445.AM2017-1537