ABERRANT METHYLATION OF PROMOTER REGIONS OF SOX7, P15INK4B AND WNT PATHWAY ANTAGONIST GENES IN PATIENTS WITH MYELODYSPLASTIC SYNDROME

DOI: https://doi.org/None

Kostroma I.I., Gritsaev S.V., Sidorova Zh.Yu., Tiranova S.A., Svitina S.P., Drizhun Yu.S., Martinkevitch I.S., Abdulkadyrov K.M., Kapustin S.I., Chechetkin A.V.

Introduction. Hypermethylation of CpG islands in tumor-suppressor genes are supposed to be a key mechanism of the development of the myelodysplastic syndrome (MDS) The aim of the study. To determine the association between methylation status of SOX7, p15INK4b, SFRP1, SFRP4 and SFRP5 genes and hematological features and overall survival (OS). Methods. Methylation-specific PCR was used to study the methylation status. Results. Aberrant methylation of ≥1 genes was found in 43/46 patients. The most frequently findings were SOX7 (84,8%), SFRP1 (71,7%) and p15INK4b (54,3%) genes methylation. There was no difference in the number of patients with SFRP1, SFRP4, SOX7 and p15INK4b methylation in the groups with different bone marrow blasts counts. Methylation of SFRP5 gene was seen more frequently in patients with refractory anemia with the excess of blasts (RAEB): 43,5% vs 13,0% in patients without excess of blasts; ОR=5,1, 95% CI: 1,2–22,3; p=0,047.The patients without excess of blasts were characterized by methylation of 0–1 genes: 26,1% vs 8.7% of RAEB patients, although the difference was not significant. There was the tendency to increase of the number of cases with 3–5 methylated genes in patients 10–19% blasts if compared to patients with 5–9% blasts. We did not find any correlation between the number of methylated genes and patient age, number of bone marrow blasts or karyotype. The increased number of methylated genes did not influence on the OS in the group of MDS patients. Conclusion. We conclude that MDS progression is associated with the enhancement of epigenetic disturbances leading to the increase of the number of methylated genes, in particular, SFRP5.
Keywords: 
myelodysplastic syndrome, methylation, gene, SOХ7, p15INK4b, SFRP1, SFRP4, SFRP5
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