Clinical significance of mutations in the NRAS, KRAS, and BRAF genes in patients with multiple myeloma

Multiple myeloma (MM) is a heterogeneous disease that undergoes a multi-stage process of cell transformation in its development, including changes in the genetic profile due to additional events such as somatic mutations, epigenetic and chromosomal changes, which leads to the emergence of a pathological clone.

To identify mutations in the NRAS, KRAS, and BRAF genes, DNA isolated from bone marrow samples of 55 patients with newly diagnosed MM was used. The studies were carried out using real-time PCR, melting curve analysis and electrophoresis analysis.

Among the examined patients with newly diagnosed MM, the mutation frequency for the NRAS gene ranged from 20,00% to 23,64%. For the KRAS gene, the frequency ranged from 16,36% to 30,91%. For the BRAF gene, the frequency was 21,82%. A combination of two mutations was detected in 16.36% of cases, and three mutations were found in 7,27% of the examined patients. In patients with MM, mutations in the KRAS gene were more common among patients with IgA secretion, bone lesions without extramedullary foci, as well as with multiple bone lesion and the presence of extramedullary lesions in the presence of the mutant T allele. No reliable associations with clinical and laboratory parameters were established between the detection of mutations in the BRAF and NRAS genes. However, the combined carriage of polymorphisms c.1799T>A in the BRAF gene and 181C>A in the NRAS gene was recorded in patients with a worse prognosis. Patients with a combination of KRAS/NRAS mutations at the time of primary diagnosis had a more aggressive course of the disease and lower progressionfree survival.

A high prevalence of mutations in the NRAS, KRAS, and BRAF genes has been established in patients with newly diagnosed myeloma. Studies have revealed an association between the studied mutations in the NRAS, KRAS, and BRAF genes and certain clinical and laboratory parameters and the course of MM.

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