Evaluation of Heterozygosity Loss in STR-Loci of Tumor DNA in Multiple Myeloma Patients with Plasmacytoma Based on the Molecular Analysis of Complex Archival Tumor Samples

Abstract

Background. Multiple myeloma (MM) is a hematological malignancy with plasma cells as substrate. Sometimes MM is characterized by plasmacytomas, i.e., intra- and extraosse-ous tumors. A paraffin block containing plasmacytoma substrate provides valuable material to be used for analyzing the molecular biological characteristics of tumor. STR-profil-ing is a method for simultaneous evaluation of DNA degradation and integral assessment of tumor genome stability. Aim. To describe STR-profiles of plasmacytoma DNA isolated from archival samples and to assess the integral stability of tumor genome against control DNA of patients. Materials & Methods. The retrospective study enrolled 10 MM patients with plasmacytoma (7 women and 3 men) aged 34-62 years (median 53.5 years) who were treated at the National Research Center for Hematology from 2013 to 2021. Paired tumor/control DNA samples were obtained from all 10 patients. Results. The present paper takes the first step in attempting a large-scale molecular genetic study of MM and provides first findings on the loss of heterozygosity (LOH) in plasmacytoma genome. All 10 patients showed LOH variants with different allelic loads having either deletion/ quantitatively neutral LOH or duplication of one of the two alleles and involving 1-8 STR-loci. In plasmacytoma substrate the number of loci with LOH tended to be higher in the group with MM relapses compared with plasmacytomas identified at disease onset. According to the data analysis, LOH was frequently (in 4 out of 10 cases) detected on chromosomes 1 (1q42), 6 (6q14), 7 (7q21.11), 13 (13q31.1), and 21 (21q21.1). Conclusion. The present paper shows the effectiveness of molecular analysis of DNAs being isolated from complex archival material consisting of paraffin blocks with plasmacytomas.