Somatic mutation analyses in studies of the clonal evolution and diagnostic targets of prostate cancer

Mikhaylenko DS, Efremov GD, Strelnikov VV, Zaletaev DV, Alekseev BY. Abstract Prostate cancer (PC) is the most common uro-oncological disease in the global population and still requires a more efficient laboratory diagnosis. Point mutations of oncogenes and tumor sup-pressor genes are the most frequent molecular genetic events in carcinogenesis. The mutations are re-sponsible, to a great extent, for the clonal evolution of cancer and can be considered as primary candi-date molecular markers of PC. Using next-generation sequencing to analyze the mutations in PC, the main molecular PC subtypes were identified, which depended on the presence of fusion genes and FOXA1, CHD1, and SPOP point mutations; other driver mutations responsible for the progression of PC subclones were also characterized. This review summarizes the data on early PC genetic markers (an mtDNA deletion, and TMPRSS2:ERG expression), as well as these somatic mutations at later stages of PC. Emphasis is placed on a switch in AR synthesis to a constitutively active variant and the point muta-tions that facilitate PC transition to a castration-refractory state that is resistant to new AR inhibitors. Based on the current whole-exome sequencing data, the frequencies and localizations of the somatic mu-tations that may provide new genetic diagnostic markers and drug targets are described. KEYWORDS: Clonal evolution; Diagnostics; Oncogene; Prostate cancer; Somatic mutation; Targeted therapy PMID: 28659719 PMCID: PMC5476950 DOI: 10.2174/1389202917666161102095900 https://www.sechenov.ru/science_and_innovation/repo/?PAGEN_1=17#134826