Division of Hematology, Department of Medicine, 65106Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, Thailand.
Technol Cancer Res Treat. 2022 Jan-Dec;21:15330338221111228. doi: 10.1177/15330338221111228.
Multiple myeloma is an incurable malignancy of plasma cells resulting from impaired terminal B cell development. Almost all patients with multiple myeloma eventually have a relapse. Many studies have demonstrated the importance of the various genomic mutations that characterize multiple myeloma as a complex heterogeneous disease. In recent years, next-generation sequencing has been used to identify the genomic mutation landscape and clonal heterogeneity of multiple myeloma. This is the first study, a prospective observational study, to identify somatic mutations in plasma cell disorders in the Thai population using targeted next-generation sequencing. Twenty-seven patients with plasma cell disorders were enrolled comprising 17 cases of newly diagnosed multiple myeloma, 5 cases of relapsed/refractory multiple myeloma, and 5 cases of other plasma cell disorders. The pathogenic mutations were found in 17 of 27 patients. Seventy percent of those who had a mutation (12/17 patients) habored a single mutation, whereas the others had more than one mutation. Fifteen pathogenic mutation genes were identified: , and . Most have previously been reported to be involved in the RAS/MAPK pathway, the nuclear factor kappa B pathway, the DNA-repair pathway, the CRBN pathway, tumor suppressor gene mutation, or an epigenetic mutation. However, the current study also identified mutations that had not been reported to be related to myeloma: and . Therefore, a deep understanding of molecular genomics would inevitably improve the clinical management of plasma cell disorder patients, and the increased knowledge would ultimately result in better outcomes for the patients.
多发性骨髓瘤是一种不可治愈的浆细胞恶性肿瘤，源于成熟 B 细胞发育受损。几乎所有多发性骨髓瘤患者最终都会复发。许多研究表明，各种基因组突变对多发性骨髓瘤作为一种复杂异质性疾病的特征具有重要意义。近年来，下一代测序已被用于鉴定多发性骨髓瘤的基因组突变景观和克隆异质性。这是第一项使用靶向下一代测序在泰国人群中鉴定浆细胞疾病体细胞突变的前瞻性观察研究。共纳入 27 例浆细胞疾病患者，包括 17 例初诊多发性骨髓瘤、5 例复发/难治性多发性骨髓瘤和 5 例其他浆细胞疾病。在 27 例患者中有 17 例发现了致病性突变。有突变的患者中，70%（12/17 例）存在单个突变，其余患者存在多个突变。共鉴定出 15 个致病突变基因：、和。大多数先前已被报道与 RAS/MAPK 通路、核因子 κB 通路、DNA 修复通路、CRBN 通路、肿瘤抑制基因突变或表观遗传突变有关。然而，本研究还鉴定出了以前未报道与骨髓瘤相关的突变：和。因此，深入了解分子基因组学必将改善浆细胞疾病患者的临床管理，增加的知识最终将为患者带来更好的结果。
