MM-1133: DNA Methylation Genes in Multiple Myeloma: A Serious Problem or a New Therapeutic Option?

The past 20 years have witnessed a significant expansion of the arsenal of diagnostic methods and the introduction of innovative approaches to analyze the genome and transcriptome of tumor cells. However, the roles of aberrant DNA methylation patterns or DNA methylation modifiers in multiple myeloma (MM) development, progression, and relapse remain unexplored. Identification of mutations by next-generation sequencing (NGS) that contribute to MM progression and the emergence of drug resistance creates specific targets for therapy. Study the prognostic significance of gene mutations in patients with MM using NGS analysis. All patients underwent mutation screening using an NGS panel of 118 genes. Patient DNA analysis was performed on the NextSeq Illumina platform using the pairedend read method. Fisher or chi-square tests were used to compare the response pattern according to sample size. Comparative survival between high-risk and low-risk groups was analyzed using the Kaplan-Meier method and the log-rank test. A study was performed in 45 patients aged 38 to 81 years (median age, 60 years). The median follow-up was 32.8 months with a maximum follow-up period of 13 years. In survival analysis, mutations in DNA methylation genes ( DNMT3A , TET2 ) showed no significant clinical significance with regard to overall survival (OS) and progression-free survival (PFS). Mutations in those genes did not influence the formation of objective response to therapy. The OS for patients with mutations in NOTCH1 was 27.3% (95% CI, 8%–83.5%) and in ATM was 59% (95% CI, 42.3%–82.9%). In Kaplan-Meier survival analysis, the presence of at least one mutation in NOTCH1 gave OS of 64% (95% CI, 42.7%–96.4%) and in ATM gave OS of 95% (95% CI, 87%–100%). The role of mutational status of DNA methylation genes is not fully understood. In our study, mutations of DNMT3A and TET2 genes did not influence the formation of objective response and did not affect the OS and PFS indices. The presence of mutations in ATM and NOTCH1 genes significantly worsened the prognosis of patients with MM.