Abstract 1614: Identification of FBXL4 as a bone metastasis-associated gene in prostate cancer

Prostate cancer (PCa) is the most common cancer among men in Western developed countries. While the majority of PCa diagnosed by PSA screening are indolent, advanced and metastatic disease has a significant mortality and morbidity. Bone metastases are extremely common in PCa and identification of bone metastasis associated genes may provide insights into PCa progression and assist in finding new drug targets. However, the genetic study of bone metastases is very limited due to the difficulty of sampling. By analyzing PCa bone metastases using high density microarrays, we found a common genomic copy number loss at 6q16.1-16.2, containing the FBXL4 gene, which was confirmed in a separate and larger series of bone metastatic samples by fluorescence in situ hybridization (FISH). Loss of FBXL4 was also detected in primary PCa, although at a significantly lower frequency than in bone metastases, and it was highly associated with prognostic factors including high Gleason score, clinical stage, PSA and extent of disease, as well as poor patient survival in conservatively-managed localized PCa, suggesting that loss of FBXL4 contributes to PCa progression. We also demonstrated that FBXL4 deletion is detectable in circulating tumor cells, making it a potential disease prognostic or progression monitoring biomarker by ‘liquid biopsy’. Consistent with loss of FBXL4 being associated with aggressive tumors, we demonstrated in vitro that FBXL4 plays a role in regulating the migration and invasion of PCa cells. Therefore, FBXL4 is a potential novel PCa suppressor gene, which may prevent cancer progression and bone metastasis through controlling cell invasion. Citation Format: Elzbieta Stankiewicz, Xueying Mao, D Chas Mangham, Lei Xu, Gabrielle Fisher, Bernard North, Henrik Moller, Peter Scardino, Jack Cuzick, Dan Berney, Yong-Jie Lu. Identification of FBXL4 as a bone metastasis-associated gene in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1614.