Poluben L., Bhasin M., Voznesensky O., Adam M., Fraenkel E., Rasnic R., Linial M., Klymenko S., Balk S. P., Fraenkel P. G.

MEDICAL GENETICS

Scentific article

Ionizing radiation (IR) is a known carcinogen that causes solid tumors and hematologic malignancies, including chronic Ph-negative myeloproliferative neoplasms (MPN). After exposure to low doses of IR delayed effects arise several months or years later. These effects are not dose-dependent (nondeterministic, or stochastic effects). It is known, the occurrence of hereditary diseases, solid tumors and hematologic neoplasms is related to stochastic events. Genomic alterations that result in the development of delayed IR effects appear immediately after exposure. These include base damages and changes, cross linking, single-strand breaks, and double-strand breaks. The aim of the study was to identify IR-induced genomic alterations which predisposed to and were involved in the disease development in MPN patients exposed to IR due to Chernobyl nuclear accident. In the study we enrolled 12 IR-exposed and 16 unexposed MPN patients, 96 healthy people who were previously exposed to IR and 89 healthy people without such history. Libraries for targeted sequencing were generated from genomic DNA of peripheral blood granulocytes using the SureSelectXT2 Target Enrichment System for Illumina Paired-End Multiplexed Sequencing kit (Agilent Technologies, Santa Clara, CA, USA), according to manufacturer’s recommendations. Common and unique sequence variants detected in both, IRexposed MPN patients and 96 healthy people previously exposed to IR were further analyzed. The identified sequence variants were not found among unexposed patients and 89 healthy unexposed people. In the presented study, significant number of sequence variants were found among genes involved in DNA transcription: PRDM16, GATA2, BCORL1, JARID2, PEG3 and PER1. We showed that PRDM16, GATA2 and BCORL1 gene changes were more frequent in IR-exposed MPN patients compared to healthy controls (58.3% vs. 6.3%, p <0.001, 25.0% vs. 4.2%, p = 0.029 and 25.0% vs. 3.1%, p = 0.018, respectively). The majority of identified sequence variants are reported in the Single Nucleotide Polymorphism Database, but their minor allele frequencies do not exceed 1% in the general population according to the Exome Aggregation Consortium. Thus, the study revealed several gene variants which might be the IR-induced alterations due to Chernobyl nuclear accident involved in the disease development in IR-exposed MPN patients.

ionizing radiation, sequence variant, gene, myeloproliferative neoplasm

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«Bulletin of problems biology and medicine» Issue 1 Part 1 (148), 2019 year, 207-210 pages, index UDK 591.156:575.113:616-005.6:616.155.191

10.29254/2077-4214-2019-1-1-148-207-210