Genetic characteristics of SARS-CoV-2 virus variants observed upon three waves of the COVID-19 pandemic in Ukraine between February 2021-January 2022.

The aim: of our study was to identify and characterize the SARS-CoV-2 variants in COVID-19 patients' samples collected from different regions of Ukraine to determine the relationship between SARS-CoV-2 phylogenetics and COVID-19 epidemiology. Patients and methods: Samples were collected from COVID-19 patients during 2021 and the beginning of 2022 (401 patients). The SARS-CoV-2 genotyping was performed by parallel whole genome sequencing. Results: The obtained SARS-CoV-2 genotypes showed that three waves of the COVID-19 pandemic in Ukraine were represented by three main variants of concern (VOC), named Alpha, Delta and Omicron; each VOC successfully replaced the earlier variant. The VOC Alpha strain was presented by one B.1.1.7 lineage, while VOC Delta showed a spectrum of 25 lineages that had different prevalence in 19 investigated regions of Ukraine. The VOC Omicron in the first half of the pandemic was represented by 13 lines that belonged to two different clades representing B.1 and B.2 Omicron strains. Each of the three epidemic waves (VOC Alpha, Delta, and Omicron) demonstrated their own course of disease, associated with genetic changes in the SARS-CoV-2 genome. The observed epidemiological features are associated with the genetic characteristics of the different VOCs, such as point mutations, deletions and insertions in the viral genome. A phylogenetic and transmission analysis showed the different mutation rates; there were multiple virus sources with a limited distribution between regions. Conclusions: The evolution of SARS-CoV-2 virus and high levels of morbidity due to COVID-19 are still registered in the world. Observed multiple virus sourses with the limited distribution between regions indicates the high efficiency of the anti-epidemic policy pursued by the Ministry of Health of Ukraine to prevent the spread of the epidemic, despite the low level of vaccination of the Ukrainian population.

Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis.

A significant need for reliable and accurate cancer diagnostics and prognosis compels the search for novel biomarkers that would be able to discriminate between indolent and aggressive tumors at the early stages of disease. The aim of this work was identification of potential diagnostic biomarkers for characterization of different types of prostate tumors. NotI-microarrays with 180 clones associated with chromosome 3 genes/loci were applied to determine genetic and epigenetic alterations in 33 prostate tumors. For 88 clones, aberrations were detected in more than 10% of tumors. The major types of alterations were DNA methylation and/or deletions. Frequent methylation of the discovered loci was confirmed by bisulfite sequencing on selective sampling of genes: FGF12, GATA2, and LMCD1. Three genes (BHLHE40, BCL6, and ITGA9) were tested for expression level alterations using qPCR, and downregulation associated with hypermethylation was shown in the majority of tumors. Based on these data, we proposed the set of potential biomarkers for detection of prostate cancer and discrimination between prostate tumors with different malignancy and aggressiveness: BHLHE40, FOXP1, LOC285205, ITGA9, CTDSPL, FGF12, LOC440944/SETD5, VHL, CLCN2, OSBPL10/ZNF860, LMCD1, FAM19A4, CAND2, MAP4, KY, and LRRC58. Moreover, we probabilistically estimated putative functional relations between the genes within each set using the network enrichment analysis.

Tumor Suppressor Function of the SEMA3B Gene in Human Lung and Renal Cancers.

The SEMA3B gene is located in the 3p21.3 LUCA region, which is frequently affected in different types of cancer. The objective of our study was to expand our knowledge of the SEMA3B gene as a tumor suppressor and the mechanisms of its inactivation. In this study, several experimental approaches were used: tumor growth analyses and apoptosis assays in vitro and in SCID mice, expression and methylation assays and other. With the use of the small cell lung cancer cell line U2020 we confirmed the function of SEMA3B as a tumor suppressor, and showed that the suppression can be realized through the induction of apoptosis and, possibly, associated with the inhibition of angiogenesis. In addition, for the first time, high methylation frequencies have been observed in both intronic (32-39%) and promoter (44-52%) CpG-islands in 38 non-small cell lung carcinomas, including 16 squamous cell carcinomas (SCC) and 22 adenocarcinomas (ADC), and in 83 clear cell renal cell carcinomas (ccRCC). Correlations between the methylation frequencies of the promoter and the intronic CpG-islands of SEMA3B with tumor stage and grade have been revealed for SCC, ADC and ccRCC. The association between the decrease of the SEMA3B mRNA level and hypermethylation of the promoter and the intronic CpG-islands has been estimated in renal primary tumors (P < 0.01). Using qPCR, we observed on the average 10- and 14-fold decrease of the SEMA3B mRNA level in SCC and ADC, respectively, and a 4-fold decrease in ccRCC. The frequency of this effect was high in both lung (92-95%) and renal (84%) tumor samples. Moreover, we showed a clear difference (P < 0.05) of the SEMA3B relative mRNA levels in ADC with and without lymph node metastases. We conclude that aberrant expression and methylation of SEMA3B could be suggested as markers of lung and renal cancer progression.