Abstract
Background. The correct genome replication is essential for normal cell division to guarantee that genetic information comes changeless through the next cells generations. DNA replication is a strictly regulated and synchronous process and its disturbances could result to mutations appearances. Aberrant time of DNA replication affects on gene expression causes changes of epigenetic modifications and influences on increasing the structural rearrangements leading to enhanced genome disbalance. Replication time failure as asynchronous replication is common for cancerogeneses. The objective of our study was the assessment of asynchronous replication levels in patients with gastric cancer and patients with multiple tumors.Materials and methods. Fluorescence in situ hybridization (FISH) was used for the asynchronous replication of AURKA and TP53 genes analyses. Interphase FISH on lymphocytes of peripheral blood of 37 healthy donors, 19 patients with non-cancer gastrointestinal pathologies, 68 patients with solitary gastric cancer and 39 patients with multiple tumors having gastric cancer and other second synchronous or metachronous tumor was carried out.Results. Values of lymphocytes with asynchronous replication for AURKA were 19.8 ± 0.5 % for control group, 24.7 ± 0.4 % for non-cancer patients, 32.5 ± 0.5 % for gastric cancer patients, 39.5 ± 0.6 % for patients with multiple tumors and 17.3 ± 0.5, 19.5 ± 0.7, 26.1 ± 0.7 and 32.5 ± 0.6 % for TP53 respectively. Differences between cell populations of examined groups had statistical significance with p <0.01 for both studied gene. Also there was statistical difference between gastric cancer patients having distant metastases and gastric cancer patients without metastases for AURKA (34.4 ± 1.0 % vs. 31.7 ± 0.6 %; p = 0.02).Conclusion. High lymphocytes with asynchronous replication level in oncological patients could serve as potential marker of second tumor or possible metastatic process including the earliest stage of it.
Highlights
The correct genome replication is essential for normal cell division to guarantee that genetic information comes changeless through the cells generations
DNA replication is a strictly regulated and synchronous process and its disturbances could result to mutations appearances
Aberrant time of DNA replication affects on gene expression causes changes of epigenetic modifications and influences on increasing the structural rearrangements leading to enhanced genome disbalance
Summary
Цель исследования – изучение встречаемости лимфоцитов периферической крови с асинхронной репликацией генов AURKA и TP53 у больных раком желудка и больных с полинеоплазиями. Доля лимфоцитов с асинхронной репликацией гена AURKA составила 19,8 ± 0,5 % для контрольной группы, 24,7 ± 0,4 % для группы с неопухолевой патологией, 32,5 ± 0,5 % для группы больных раком желудка и 39,5 ± 0,6 % для группы с полинеоплазиями; для гена TP53 – 17,3 ± 0,5; 19,5 ± 0,7; 26,1 ± 0,7 и 32,5 ± 0,6 % соответственно. Больные раком желудка с метастазами имели бόльшую долю лимфоцитов с асинхронной репликацией гена AURKA, чем пациенты без метастазов (34,4 ± 1,0 % против 31,7 ± 0,6; p = 0,02). Асинхронная репликация генов AURKA и TP53 у больных солитарным раком желудка и больных с полинеоплазиями. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center, Ministry of Health of Russia; 4 Koroleva St., Obninsk 249031, Russia
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