Loss of Heterozygosity and Mutations in the RAS-ERK Pathway Genes in Tumor Cells of Various Loci in Multiple Myeloma

• Published in: International journal of molecular sciences Vol. 25; no. 17; p. 9426
• Main Authors: Soloveva, Maiia, Solovev, Maksim, Risinskaya, Natalya, Nikulina, Elena, Yakutik, Igor, Biderman, Bella, Obukhova, Tatiana, Chabaeva, Yulia, Kulikov, Sergej, Sudarikov, Andrey, Mendeleeva, Larisa
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.08.2024
• Subjects: Adult; Aged; Aged, 80 and over; Biopsy; Bone marrow; Circulating Tumor DNA - blood; Circulating Tumor DNA - genetics; Cloning; Female; free circulating tumor DNA in plasma; Genes; GTP Phosphohydrolases - genetics; Humans; liquid biopsy; Liquid Biopsy - methods; loss of heterozygosity; Male; MAP Kinase Signaling System - genetics; Medical prognosis; Membrane Proteins - genetics; Middle Aged; Multiple myeloma; Multiple Myeloma - genetics; Multiple Myeloma - pathology; Mutation; Patients; plasmacytoma; Prospective Studies; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras) - genetics; STR profile; BRAF genes; NRAS; multiple myeloma; STR profile; plasmacytoma; KRAS; loss of heterozygosity; free circulating tumor DNA in plasma; liquid biopsy
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25179426

Multiple myeloma (MM) is a disease characterized by spatiotemporal heterogeneity of tumor clones. Different genetic aberrations can be observed simultaneously in tumor cells from different loci, and as the disease progresses, new subclones may appear. The role of liquid biopsy, which is based on the analysis of tumor DNA circulating in the blood plasma, continues to be explored in MM. Here, we present an analysis of the STR profiles and mutation status of the , , and genes, evaluated in plasma free circulating tumor DNA (ctDNA), CD138+ bone marrow cells, and plasmacytomas. The prospective single-center study included 97 patients, with a median age of 55 years. Of these, 94 had newly diagnosed symptomatic MM, and three had primary plasma cell leukemia. It should be noted that if mutations were detected only in ctDNA, "non-classical" codons were more often affected. A variety of adverse laboratory and clinical factors have been associated with the detection of rare or gene mutations in bone marrow or ctDNA, suggesting that these mutations may be factors of an unfavorable prognosis for MM. Liquid biopsy studies provide undeniable fundamental information about tumor heterogeneity and clonal evolution in MM. Moreover, we focus on using liquid biopsy to identify new high-risk factors for MM.