Loss of Heterozygosity in the Circulating Tumor DNA and CD138+ Bone Marrow Cells in Multiple Myeloma

Abstract

Multiple myeloma (MM) is characterized by heterogeneity of tumor cells. The study of tumor cells from blood, bone marrow, plasmacytoma, etc., allows us to identify similarities and differences in tumor lesions of various anatomical localizations. The aim of this study was to compare the loss of heterozygosity (LOH) by tumor cells by assessing STR profiles of different MM lesions. We examined paired samples of plasma circulating tumor DNA (ctDNA) and CD138+ bone marrow cells in MM patients. For patients with plasmacytomas (66% of 38 patients included), the STR profile of plasmacytomas was also studied when biopsy samples were available. Diverse patterns of LOH were found in lesions of different localization for most patients. LOH in plasma ctDNA, bone marrow, and plasmacytoma samples was found for 55%, 71%, and 100% of patients, respectively. One could expect a greater variety of STR profiles in aberrant loci for patients with plasmacytomas. This hypothesis was not confirmed—no difference in the frequency of LOH in MM patients with or without plasmacytomas was found. This indicates the genetic diversity of tumor clones in MM, regardless of the presence of extramedullar lesions. Therefore, we conclude that risk stratification based on molecular tests performed solely on bone marrow samples may not be sufficient for all MM patients, including those without plasmacytomas. Due to genetic heterogeneity of MM tumor cells from various lesions, the high diagnostic value of liquid biopsy approaches becomes obvious.

Accumulation of STR-Loci Aberrations in Subclones of Jurkat Cell Line as a Model of Tumor Clonal Evolution

“…This robust research tool provides information on a variety of changes in the genome, including chromosome aberrations and small deletions and insertions of several nucleotides. Previously, we studied the STR profiles of tumor cells in patients with acute lymphoblastic leukemia, B-cell lymphomas, and multiple myeloma and observed two types of aberrations—loss of heterozygosity (LOH) and elevated microsatellite alteration at selected tetranucleotide repeats (EMAST) [ 13 , 14 , 15 , 16 ]. When verified by the microarray, the STR loci with LOH were always in the region of large deletions or a copy neutral loss of heterozygosity.…”

“…Sometimes new aberrations were added to the genetic profile in the recurrence of ALL. In multiple myeloma with plasmacytoma, differences in DNA profiles from plasmacytoma and bone marrow CD138+ cells were also observed [ 15 , 16 ]. Currently, many works are devoted to chemotherapy-induced clonal evolution.…”