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.
多发性骨髓瘤是一种由浆细胞异常增殖引起的血液系统肿瘤。测序研究表明，浆细胞疾病是由细胞遗传学异常和癌基因突变共同导致的。因此，检测分子异常对于改善多发性骨髓瘤的诊断和治疗管理至关重要。本研究的主要目的是确定除细胞遗传学检测外，二代测序技术是否能够影响风险分层和治疗策略。此外，我们旨在明确与整体细胞群相比，对CD138细胞群进行突变分析是否为多发性骨髓瘤特征鉴定的合适选择。通过对35例新诊断多发性骨髓瘤患者的浆细胞进行分离，我们采用荧光原位杂交技术检测了最常见的染色体异常。随后，我们使用二代测序技术评估了浆细胞群及骨髓样本中的NRAS、KRAS、BRAF和TP53基因突变。二代测序数据显示，对CD138细胞进行测序能提供更灵敏的检测方法。我们在BRAF、KRAS和TP53基因中发现了多个先前未与多发性骨髓瘤相关的变异。鉴于体细胞突变的存在可能影响多发性骨髓瘤患者的风险分层和治疗方案，在诊断时对这些突变进行灵敏检测对于多发性骨髓瘤的优化管理至关重要。
肿瘤(癌症)患者之家