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 suppressor
genes are the most frequent molecular genetic events in carcinogenesis. The mutations are responsible,
to a great extent, for the clonal evolution of cancer and can be considered as primary candidate
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 mutations 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 mutations that may provide new genetic diagnostic markers and drug targets are described.
Keywords: Oncogene, Somatic mutation, Clonal evolution, Prostate cancer, Diagnostics, Targeted therapy.
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