1. Somatic mutation analyses in studies of the clonal evolution and diagnostic targets of prostate cancer
- Author
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Mikhaylenko DS
- 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  
- Published
- 2018