Non-coding and coding genomic variants distinguish prostate cancer, castration-resistant prostate cancer, familial prostate cancer, and metastatic castration-resistant prostate cancer from each other.

A considerable number of deposited variants has provided new possibilities for knowledge discovery in different types of prostate cancer. Here, we analyzed variants located on 3'UTR, 5'UTR, CDs, Intergenic, and Intronic regions in castration-resistant prostate cancer (8496 variants), familial prostate cancer (3241 variants), metastatic castration-resistant prostate cancer (3693 variants), and prostate cancer (16599 variants). Chromosome regions 10p15-p14 and 2p13 were highly enriched (P < 0.00001) for variants located in 3'UTR, 5'UTR, CDs, intergenic, and intronic regions in castration-resistant prostate cancer. In contrast, 10p15-p14, 10q23.3, 12q13.11, 13q12.3, 1q25, and 8p22 regions were enriched (P < 0.001) in familial prostate cancer. In metastatic castration-resistant prostate cancer, 10p15-p14, 10q23.3, 11q22-q23, 14q21.1, and 14q32.13 were highly variant regions (P < 0.001). Chromosome 2 and chromosome 1 hosted many enriched variant regions. AKR1C3, BRCA1, BRCA2, CHGA, CYP19A1, HOXB13, KLK3, and PTEN contained the highest number of 3'UTR, 5'UTR, CDs, Intergenic, and Intronic variants. Network analysis showed that these genes are upstream of important functions including prostate gland development, tumor recurrence, prostate cancer-specific survival, tumor progression, cancer mortality, long-term survival, cancer recurrence, angiogenesis, and AR. Interestingly, all of EGFR, JAK2, NR3C1, PDZD2, and SEMA3C genes had single nucleotide polymorphisms (SNP) in castration-resistant prostate cancer, consistent with high selection pressure on these genes during drug treatment and consequent resistance. High occurrence of variants in 3'UTRs suggests the importance of regulatory variants in different types of prostate cancer; an area that has been neglected compared with coding variants. This study provides a comprehensive overview of genomic regions contributing to different types of prostate cancer.

Molecular carcinogenesis. 2019 Jan 15 [Epub ahead of print]

Ibrahim O Alanazi, Zafer S Al Shehri, Esmaeil Ebrahimie, Hassan Giahi, Manijeh Mohammadi-Dehcheshmeh

National Center for Biotechnology, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia., Clinical Laboratory Department, College of Applied Medical Sciences, Shaqra University, KSA, Al dawadmi, Saudi Arabia., Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia., Institute of Biotechnology, Shiraz University, Shiraz, Iran., Australian Centre for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, The University of Adelaide, South Australia, Australia.