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. 2021;13(3):33-38.
doi: 10.17691/stm2021.13.3.04. Epub 2021 Jun 28.

Asynchronous DNA Replication of Biallelically Expressed Genes in Human Peripheral Blood Lymphocytes as a Prognostic Sign of Cancer

V V Tsepenko  1 , T G Shkavrova  1 , V N Cherkesov  2 , E V Golub  3 , G F Mikhailova  4
Affiliations

Asynchronous DNA Replication of Biallelically Expressed Genes in Human Peripheral Blood Lymphocytes as a Prognostic Sign of Cancer

V V Tsepenko et al. Sovrem Tekhnologii Med. 2021.

Abstract

The aim of the study was to identify and quantify lymphocytes with asynchronous replication of the AURKA and TP53 genes in cancer patients versus controls and to assess the diagnostic capabilities of this approach.

Materials and methods: The study was carried out with peripheral blood lymphocytes probed for the AURKA and TP53 genes using the interphase fluorescence in situ hybridization (FISH) method (Vysis, USA and Kreatech, The Netherlands). The control group included 70 people: clinically healthy donors and patients with non-oncological diseases such as gastritis, pancreatitis, chronic calculous cholecystitis, bronchial asthma, peptic ulcer disease, inguinal hernia, arthrosis, myoma, hepatitis, epilepsy, chronic prostatitis, chronic tonsillitis, and rectal adenoma. The group of cancer patients included 219 people with various oncological diseases: gastric cancer (n=68), colorectal cancer (n=30), chronic lymphocytic leukemia (n=52), Hodgkin lymphoma (n=33), and polyneoplasia (n=41).

Results: In the control group, the mean frequency of lymphocytes with asynchronous gene replication (AGR) was 22.0±3.4% for AURKA and 18.0±3.2% for TP53; in the group of cancer patients, that was 36.8±4.8 and 28.4±5.1%, respectively. The excessive presence of lymphocytes with the AGR in cancer patients was consistent and statistically significant (p<0.0001). For the AURKA gene, the AGR-based cancer detection showed a sensitivity of 98.6±0.7%, a specificity of 100%, and an accuracy of 98.3±0.8%, and for the TP53 gene - 78.6±3.1, 98.5±0.9, and 85.9±2.6%, respectively.

Conclusion: This pilot study on lymphocytes with AGR of AURKA and TP53 genes in cancer patients can serve a basis for creating a new molecular cytogenetic technology for detecting malignant neoplasms in humans.

Keywords: AURKA; FISH; TP53; asynchronous DNA replication; diagnosis of malignant neoplasms; fluorescence in situ hybridization; peripheral blood lymphocytes.

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Conflict of interest statement

Conflicts of interest. The authors have no conflicts of interest related to this publication.

Figures

Figure 1
Figure 1. Asynchronous replication of the TP53 gene in human peripheral blood lymphocytes:
(a) normal lymphocyte (two single signals); (b) lymphocyte with impaired synchronicity of gene replication (one single and one double signal); ×1000
Figure 2
Figure 2. The mean frequency for lymphocytes with asynchronous replication of the AURKA and TP53 genes in the control group and in cancer patients. Two-sided Student’s t-test; M±σ; p<0.05
See this image and copyright information in PMC

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References

    1. Kaprin A.D., Starinskiy V.V., Petrova G.V., editors. [Malignant neoplasms in Russia in 2018 (morbidity and mortality)]. Zlokachestvennye novoobrazovaniya v Rossii v 2018 godu (zabolevaemost’ i smertnost’) Moscow: MNIOI im. A. Gertsena — filial FGBU “NMITs radiologii” Minzdrava Rossii; 2019. p. 250.
    1. Blumenfeld B., Ben-Zimra M., Simon I. Perturbations in the replication program contribute to genomic instability in cancer. Int J Mol Sci. 2017;18(6):1138. doi: 10.3390/ijms18061138. - DOI - PMC - PubMed
    1. Hiratani I., Gilbert D.M. Replication timing as an epigenetic mark. Epigenetics. 2009;4(2):93–97. doi: 10.4161/epi.4.2.7772. - DOI - PMC - PubMed
    1. Donley N., Thayer M.J. DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing is associated with increased genomic instability. Semin Cancer Biol. 2013;23(2):80–89. doi: 10.1016/j.semcancer.2013.01.001. - DOI - PMC - PubMed
    1. Ryba T., Battaglia D., Chang B.H., Shirley J.W., Buckley Q., Pope B.D., Devidas M., Druker B.J., Gilbert D.M. Abnormal developmental control of replication-timing domains in pediatric acute lymphoblastic leukemia. Genome Res. 2012;22(10):1833–1844. doi: 10.1101/gr.138511.112. - DOI - PMC - PubMed

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