The 16p13.3 (PDPK1) Genomic Gain in Prostate Cancer: A Potential Role in Disease Progression 1

BACKGROUND: Prostate cancer (PCa) is a leading cause of cancer death, and distinguishing aggressive from indolent tumors is a major challenge. Identification and characterization of genomic alterations associated with advanced disease can provide new markers of progression and better therapeutic approaches. METHODS: We performed fluorescence in situ hybridization to detect the copy number gain of chromosome 16p13.3 in 75 PCa samples including 10 lymph node (LN) metastases and their matched primary tumors, 9 samples of castration-resistant prostate cancer (CRPC), and 46 additional primary PCa specimens with clinicopathologic parameters. RESULTS: We detected the gain in 5 of 10 LN metastases and 3 of 5 matched primary tumors, 3 of 9 CRPC samples, and 9 of 46 (20%) primary tumors where the 16p13.3 alteration was associated with high Gleason score and elevated preoperative prostate-specific antigen levels. The level of 16p13.3 gain was higher in LN metastasis and CRPC specimens compared to primary PCa. Chromosome mapping revealed the gain spans PDPK1 encoding the 3-phosphoinositide-dependent protein kinase-1 (PDK1). Knockdown of PDK1 in three PCa cell lines reduced migration without affecting growth and re-expressing PDK1 rescued motility. CONCLUSION: Our findings support a prognostic value of the 16p13.3 gain and a role of PDK1 in PCa progression through migration.