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

Overview

Journal Transl Oncol

Specialty Oncology

Date 2013 Feb 13

PMID 23401739

Citations 22

Authors

Khalil A Choucair

Karl-Philippe Guerard

Joshua Ejdelman

Simone Chevalier

Maisa Yoshimoto

Eleonora Scarlata

Ladan Fazli

Kanishka Sircar

Jeremy A Squire

Fadi Brimo

Isabela W Cunha

Armen Aprikian

Martin Gleave

Jacques Lapointe

Affiliations

Soon will be listed here.

Abstract

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.

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