Aberrant methylation of promoter regions of sox7, p15ink4b and WNT pathway antago- nist genes in patients with myelodysplas- tic syndrome
Ivan I. Kostroma, Sergey V. Gritsaev, Zh. Yu. Sidorova, S. A. Tiranova, S. P. Svitina, Yulia S. Drizhun, Irina S. Martinkevitch, Kudrat M. Abdulkadyrov, Sergej I. Kapustin, Alexander V. Chechetkin
Russian Research Institute of Hematology and Transfusiology, St. Petersburg, Russian Federation
Summary
Introduction
Epigenetic aberrations, including hypermethylation of CpG islands in tumor suppressor genes, are supposed to be a key mechanism of myelodysplastic syndrome (MDS) development. The aim of study was to find out the association between methylation status of SOX7, p15INK4b, SFRP1, SFRP4 and SFRP5 genes and some hematological features and overall survival (OS).
Patients and methods
We have analyzed the data of 46 MDS patients with median age of 67.5 years were analyzed. MDS was diagnosed according to WHO classification. Methylation-specific PCR was used to study the methylation status.
Results
Aberrant methylation of ≥1 genes was found in 43 patients (93,5%). The most frequent findings was methylation of SOX7 (84,8%), SFRP1 (71,7%) and p15INK4b (54,3%) genes. The methylation of 1, 2, 3, 4 and 5 genes was detected, respectively, in 10,9%, 28,3%, 26,1%, 19,6% and 8,7% of patients. There was no any 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 more frequently seen in patients with refractory anemia with excess of blasts (RAEB): 43,5% vs 13,0% in patients without excess of blasts; OR=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. At the same time, there was a tendency for increased number of cases with 3-5 methylated genes in patients with 10-19% blasts, as compared to patients with 5-9% blasts. In total MDS group there was no correlation found between the number of methylated genes and patients’ age, number of bone marrow blasts or karyotype changes. Increased number of methylated genes did not influence the OS values among the MDS patients.
Conclusion
We conclude that MDS progression is associated with enhancement of epigenetic disturbances leading to increased number of methylated genes, in particular, SFRP5.
Keywords
Myelodysplastic syndrome, methylation, gene, soХ7, p15ink4b, sfrp1, sfrp4, sfrp5
