METHODS OF NEXT GENERATION SEQUENCING IN THE IDENTIFICATION OF MOLECULAR GENETIC DETERMINANTS OF HEPATOCARCINOGENESIS

DOI: https://doi.org/None

A.S. Makarova (1,2), I.F. Kustova (1), N.L. Lazarevich (1,2) 1 -Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center, Kashirskoe shosse, 24/15, Moscow, Russian Federation, 115478; 2 -M.V.Lomonosov Moscow State University, Leninskie gory, 1, Moscow, Russian Federation, 119234

Hepatocellular carcinoma (HCC) is the most prevalent form of malignant liver cancer characterized by late detection time and highly aggressiveness. The main risk factors for HCC development are chronic infections of hepatitis B and C viruses, cirrhosis, liver intoxication and some hereditary metabolic disorders. Hepatocarcinogenesis is multistep process, associated with multiple alterations of DNA structure and gene expression at different stages of tumor progression. These aberrations particularly affect components of Wnt/β-catenin-, р53- and Ras/MAPK-dependent signaling pathways, systems controlling chromatin remodeling and oxidative stress response. However up to the present the reliable prognostic markers for the estimation of HCC malignancy level which would allow the development of effective schemes for individualized HCC treatment choice had not been proposed. Development of the technologies of massive parallel sequencing (NGS) opens the remarkable advances in this field. Methods of exome and transcriptome sequencing allowed identification of new single nucleotide variations, deletions and insertions, chromosomal rearrangements, fusion proteins specific for tumor tissue, differential expression of genes and their alternatively spliced isoforms. The review considers the main molecular genetics aberrations specific for hepatocarcinogenesis and the prospects of NGS technology use for identification of the key determinants of hepatocyte malignant transformation which can be considered as potential targets for the development of new approaches for HCC therapy.
Keywords: 
hepatocellular carcinoma, massive parallel sequencing, mutations, chromosome aberrations, transcriptome, targeted therapy
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