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Abstract

Volume 22, Issue 2 (March 2020) 22, 162–168; 10.4103/aja.aja_36_19

Integrative molecular characterization of Chinese prostate cancer specimens

Shi-Dong Lv1,2,3, Hong-Yi Wang3, Xin-Pei Yu4, Qi-Liang Zhai3, Yao-Bin Wu1,2, Qiang Wei3, Wen-Hua Huang1,2

1 National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
    2 Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangzhou 510515, China
    3 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
    4 Department of Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, China

Correspondence: Dr. WH Huang (huangwenhua2009@139.com) or Dr. Q Wei (qwei@smu.edu.cn)

28-May-2019

Abstract

Prostate cancer (PCa) exhibits epidemiological and molecular heterogeneity. Despite extensive studies of its phenotypic and genetic properties in Western populations, its molecular basis is not clear in Chinese patients. To determine critical molecular characteristics and explore correlations between genomic markers and clinical parameters in Chinese populations, we applied an integrative genetic/transcriptomic assay that combines targeted next-generation sequencing and quantitative real-time PCR (qRT-PCR) on samples from 46 Chinese patients with PCa. Lysine (K)-specific methyltransferase 2D (KMT2D), zinc finger homeobox 3 (ZFHX3), A-kinase anchoring protein 9 (AKAP9), and GLI family zinc finger 1 (GLI1) were frequently mutated in our cohort. Moreover, a clinicopathological analysis showed that RB transcriptional corepressor 1 (RB1) deletion was common in patients with a high risk of disease progression. Remarkably, four genomic events, MYC proto-oncogene (MYC) amplification, RB1 deletion, APC regulator of WNT signaling pathway (APC) mutation or deletion, and cyclin-dependent kinase 12 (CDK12) mutation, were correlated with poor disease-free survival. In addition, a close link between KMT2D expression and the androgen receptor (AR) signaling pathway was observed both in our cohort and in The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) data. In summary, our results demonstrate the feasibility and benefits of integrative molecular characterization of PCa samples in disease pathology research and personalized medicine.
    
    Keywords: androgen receptor; molecular subtyping; next generation sequencing; prostate cancer; quantitative real-time-polymerase chain reaction

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