Analysis of Somatic Mutations in Epigenetic Genes in Major Leukemia Subtypes

Aim: In this study, we aimed to investigate the presence of somatic mutations in DNMT3A, TET1, TET2, IDH1, IDH2, ASXL1 and SETBP1 genes that play a role in epigenetic regulation by NGS analysis of bone marrow samples of 13 ALL, 19 AML, 14 CLL and 15 CML patients.. Material and Method: NA was isolated from bone marrow samples of 13 ALL, 19 AML, 14 CLL and 15 CML patients and Kapa NGS DNA extraction kit was used for sequence analysis. The purity and concentration of the DNA obtained were measured by Qubit fluoremeter, and NadPrep DNA Universal Library Preparation Kit was used for high quality library preparation. Bioinformatic analysis of the data obtained from the study was performed through the portal provided by Roche Diagnostics for NGS solutions. The pathogenicity status of the variants detected in the relevant genes was made according to the ACMG classification. Results: Variations in at least one gene were found in all but one of the 13 patients diagnosed with ALL. Among 7 genes, the most distinct variant was detected in TET3 gene and all of them were VUS variants according to ACMG classification. In 19 patients diagnosed with AML, the gene with the highest number of distinct variants was TET3 and all variants were in the VUS class, followed by TET2 and ASXL1 genes, respectively. Variants were detected in at least one gene in all but 4 AML patients. No variant was detected in 4 of 14 patients diagnosed with CLL. Variants were detected in at least one of the related genes in the remaining patients. One of the 15 patients diagnosed with CML did not have any variant in the relevant genes. In the remaining patients, variants were detected in at least one of the related genes. The genes with the highest number of distinct variants in CML patients were TET3, ASXL1 and SETBP1, respectively. Conclusion: At least one variant of the related genes was detected in all leukaemia subtypes constituting the study sample. In our study, c.856-2A>T variant in DNMT3A gene was detected in at least one patient from the patient groups with major leukaemia subtypes. This suggests that this variant may play an important role in haematopoietic stem cell processes.