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

[ Vol. 18 , Issue. 3 ]

Author(s):

Dmitry S. Mikhaylenko, Gennady D. Efremov, Vladimir V. Strelnikov, Dmitry V. Zaletaev and Boris Y. Alekseev   Pages 236 - 243 ( 8 )

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.

Affiliation:

Department of Pathology with Molecular Genetic Group, N. Lopatkin Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiological Center, P.O. Box: 105425, Moscow, Pathology Department, Molecular Genetics Group, N. Lopatkin Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Radiological Center, Moscow, Laboratory of Epigenetics, Research Centre for Medical Genetics, Moscow, Laboratory of Human Molecular Genetics, Institute of Molecular Medicine of the Sechenov First Moscow State Medical University, Moscow, Pathology Department, Molecular Genetics Group, N. Lopatkin Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Radiological Center, Moscow

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