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

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...

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Autores principales: Mikhaylenko, Dmitry S., Efremov, Gennady D., Strelnikov, Vladimir V., Zaletaev, Dmitry V., Alekseev, Boris Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bentham Science Publishers 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476950/
https://www.ncbi.nlm.nih.gov/pubmed/28659719
http://dx.doi.org/10.2174/1389202917666161102095900
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author Mikhaylenko, Dmitry S.
Efremov, Gennady D.
Strelnikov, Vladimir V.
Zaletaev, Dmitry V.
Alekseev, Boris Y.
author_facet Mikhaylenko, Dmitry S.
Efremov, Gennady D.
Strelnikov, Vladimir V.
Zaletaev, Dmitry V.
Alekseev, Boris Y.
author_sort Mikhaylenko, Dmitry S.
collection PubMed
description 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.
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spelling pubmed-54769502017-12-01 Somatic Mutation Analyses in Studies of the Clonal Evolution and Diagnostic Targets of Prostate Cancer Mikhaylenko, Dmitry S. Efremov, Gennady D. Strelnikov, Vladimir V. Zaletaev, Dmitry V. Alekseev, Boris Y. Curr Genomics Article 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. Bentham Science Publishers 2017-06 2017-06 /pmc/articles/PMC5476950/ /pubmed/28659719 http://dx.doi.org/10.2174/1389202917666161102095900 Text en © 2017 Bentham Science Publishers https://creativecommons.org/licenses/by-nc/4.0/legalcode This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
spellingShingle Article
Mikhaylenko, Dmitry S.
Efremov, Gennady D.
Strelnikov, Vladimir V.
Zaletaev, Dmitry V.
Alekseev, Boris Y.
Somatic Mutation Analyses in Studies of the Clonal Evolution and Diagnostic Targets of Prostate Cancer
title Somatic Mutation Analyses in Studies of the Clonal Evolution and Diagnostic Targets of Prostate Cancer
title_full Somatic Mutation Analyses in Studies of the Clonal Evolution and Diagnostic Targets of Prostate Cancer
title_fullStr Somatic Mutation Analyses in Studies of the Clonal Evolution and Diagnostic Targets of Prostate Cancer
title_full_unstemmed Somatic Mutation Analyses in Studies of the Clonal Evolution and Diagnostic Targets of Prostate Cancer
title_short Somatic Mutation Analyses in Studies of the Clonal Evolution and Diagnostic Targets of Prostate Cancer
title_sort somatic mutation analyses in studies of the clonal evolution and diagnostic targets of prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476950/
https://www.ncbi.nlm.nih.gov/pubmed/28659719
http://dx.doi.org/10.2174/1389202917666161102095900
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