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Can peripheral blood provide good DNA methylation biomarkers in myelodysplastic syndrome?

Year: 2021

Type: article

Abstract: Myelodysplastic syndromes (MDS) are a group of hematological stem cell malignancies strongly associated with aberrant epigenetic anomalies, namely DNA methylation. Blood-based specimens may be a potential source of noninvasive DNA methylation cancer biomarkers. Systemic methylation profile has been explored in solid tumors but is still largely unknown in hematological cancers. We compared DNA methylation status in bone marrow (BM) aspirates and peripheral blood (PB) in MDS patients at diagnosis. Using MS-PCR, we compared DNA methylation status of nine tumor suppressor genes (TSG) P15, P16, TP53, DAPK, MGMT, and TRAIL receptors (TRAIL-DcR1, -DcR2, -DR4, and -DR5) genes. Statistical analysis was performed using the chi-square test, and Kappa statistics analyzed the concordance between BM and PB methylation. Overall survival was assessed by the Kaplan-Meier method. In MDS patients, we observed a high methylation status of the analyzed genes, mainly P15 (64.7%) and DAPK (60.3%). Moreover, 75% of MDS patients presented more than two hypermethylated genes, and these patients had a significantly lower overall survival. We observed a good correlation between gene methylation patterns in PB and BM samples, mainly for P15 (70.6% concordance; kappa = 0.344) and TRAIL-DcR1 (75% concordance; kappa = 0.243). No patient presented TP53 and MGMT methylated genes. Our results suggest that DNA methylation patterns measured in PB may have great potential as informative biomarkers of MDS-related tumor suppressor genes methylation.

Source: Journal of Molecular and Clinical Medicine

DOI: 10.31083/j.jmcm.2021.01.015