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

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 MethodsThe 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).ResultsIn 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.ConclusionThis 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.