NCOR1 may be a potential biomarker of a novel molecular subtype of prostate cancer

• Published in: FEBS open bio Vol. 10; no. 12; pp. 2678 - 2686
• Main Authors: Tang, Lu, Zhang, Lixia, Liu, Lei, Dong, Liping, Dong, Yuan, Zhu, Wenhe, Wang, Huiyan
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.12.2020; John Wiley and Sons Inc
• Subjects: Age; androgen receptors; biomarkers; Biopsy; Biotechnology; Carbon dioxide; Castration; Cell culture; exons; Fluorescent indicators; Genes; genetic markers; Genomes; genomics; Lymph nodes; Lymphatic system; males; Membrane potential; Mesenchyme; Metastasis; Mitochondria; mitochondrial membrane; molecular subtype; molecular systematics; Mutation; NCOR1; Paraffin; Patients; Penicillin; Polystyrene; Prostate cancer; prostatic neoplasms; Reactive oxygen species; RNA-mediated interference; Statistical analysis; Streptomycin; Tumors; United States > US; China; prostate cancer; NCOR1; molecular subtype
• ISSN: 2211-5463; 2211-5463
• DOI: 10.1002/2211-5463.13004

Our data suggest that Nuclear receptor corepressor (NCOR1) is involved in the maintenance of mitochondrial membrane potential in prostate cancer cells, and loss of NCOR1 may contribute to prostate cancer progression. Prostate cancer (PCa) is the most frequently diagnosed male cancer. An earlier study of a cohort of 333 primary prostate carcinomas showed that 74% of these tumors fell into one of seven subtypes of a molecular taxonomy defined by specific gene fusions (ERG, ETV1/4 and FLI1) or mutations (SPOP, FOXA1 and IDH1). Molecular subtypes may aid in distinguishing indolent cases from aggressive cases and improving management of the disease. However, molecular features of PCa outside the seven subtypes are still not well studied. Here we report molecular features of PCa cases without typical features of the established subtypes. We performed comprehensive genomic analysis of 91 patients, including 54 primary and 37 metastatic cases, by whole‐exome sequencing. TP53, SPOP, FOXA1, AR (androgen receptor) and a TMPRSS2–ERG fusion emerged as the most commonly altered genes in primary cases, whereas AR, FOXA1, PTEN, CDK12, APC and TP53 were the most commonly altered genes in metastatic cases. Nuclear receptor corepressor (NCOR1) genomic alterations have been identified in 5% of cases, which are nontypical molecular features of PCa subtypes. A novel NCOR1 c.2182G>C (p.Val728Leu) was identified in tumor. RT‐PCR was used to show that this mutation caused loss of NCOR1 exon 19 and might be oncogenic in PCa. NCOR1 is involved in maintenance of mitochondrial membrane potential in PCa cells, and loss of NCOR1 might contribute to PCa progression. Therefore, NCOR1 may be a potential molecular marker of a subtype of PCa.