DNA Sequencing of CD138 Cell Population Reveals TP53 and RAS-MAPK Mutations in Multiple Myeloma at Diagnosis

Simple Summary Multiple myeloma is a hematologic neoplasm caused by abnormalities of plasma cells. Although cytogenetic-based risk stratifications are in clinical use, the role of genomic mutations in prognosis assessment is incompletely understood. Moreover, the sample source for molecular testing is a matter of debate, with recent data pointing out that seeking for mutations in plasma cells would increase the yield. We hereby compared both cytogenetic abnormalities and mutations detected by NGS in bulk bone marrow samples and CD138+ enriched plasma cells from patients diagnosed with multiple myeloma. We performed a FISH analysis, and then we used NGS to assess mutations in NRAS, KRAS, BRAF, and TP53 in the plasma cells and bulk bone marrow samples. The NGS data showed that the sequencing of the CD138+ plasma cells provided a more sensitive approach by identifying more variants in BRAF, KRAS, and TP53 compared to bulk marrow sequencing.Abstract Multiple myeloma is a hematologic neoplasm caused by abnormal proliferation of plasma cells. Sequencing studies suggest that plasma cell disorders are caused by both cytogenetic abnormalities and oncogene mutations. Therefore, it is necessary to detect molecular abnormalities to improve the diagnosis and management of MM. The main purpose of this study is to determine whether NGS, in addition to cytogenetics, can influence risk stratification and management. Additionally, we aim to establish whether mutational analysis of the CD138 cell population is a suitable option for the characterization of MM compared to the bulk population. Following the separation of the plasma cells harvested from 35 patients newly diagnosed with MM, we performed a FISH analysis to detect the most common chromosomal abnormalities. Consecutively, we used NGS to evaluate NRAS, KRAS, BRAF, and TP53 mutations in plasma cell populations and in bone marrow samples. NGS data showed that sequencing CD138 cells provides a more sensitive approach. We identified several variants in BRAF, KRAS, and TP53 that were not previously associated with MM. Considering that the presence of somatic mutations could influence risk stratification and therapeutic approaches of patients with MM, sensitive detection of these mutations at diagnosis is essential for optimal management of MM.