Somatic Mutation Analyses in Studies of the Clonal Evolution and Diagnostic Targets of Prostate Cancer

Author(s): Dmitry S. Mikhaylenko*, Gennady D. Efremov, Vladimir V. Strelnikov, Dmitry V. Zaletaev, Boris Y. Alekseev.

Journal Name: Current Genomics

Volume 18 , Issue 3 , 2017

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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 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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Article Details

VOLUME: 18
ISSUE: 3
Year: 2017
Page: [236 - 243]
Pages: 8
DOI: 10.2174/1389202917666161102095900
Price: $58

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