Department of Laboratory Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
PLoS One. 2021 Feb 5;16(2):e0246322. doi: 10.1371/journal.pone.0246322. eCollection 2021.
To investigate the prognostic value of gene variants and copy number variations (CNVs) in patients with newly diagnosed multiple myeloma (NDMM), an integrative genomic analysis was performed.
Sixty-seven patients with NDMM exhibiting more than 60% plasma cells in the bone marrow aspirate were enrolled in the study. Whole-exome sequencing was conducted on bone marrow nucleated cells. Mutation and CNV analyses were performed using the CNVkit and Nexus Copy Number software. In addition, karyotype and fluorescent in situ hybridization were utilized for the integrated analysis.
Eighty-three driver gene mutations were detected in 63 patients with NDMM. The median number of mutations per patient was 2.0 (95% confidence interval [CI] = 2.0-3.0, range = 0-8). MAML2 and BHLHE41 mutations were associated with decreased survival. CNVs were detected in 56 patients (72.7%; 56/67). The median number of CNVs per patient was 6.0 (95% CI = 5.7-7.0; range = 0-16). Among the CNVs, 1q gain, 6p gain, 6q loss, 8p loss, and 13q loss were associated with decreased survival. Additionally, 1q gain and 6p gain were independent adverse prognostic factors. Increased numbers of CNVs and driver gene mutations were associated with poor clinical outcomes. Cluster analysis revealed that patients with the highest number of driver mutations along with 1q gain, 6p gain, and 13q loss exhibited the poorest prognosis.
In addition to the known prognostic factors, the integrated analysis of genetic variations and CNVs could contribute to prognostic stratification of patients with NDMM.
为了研究基因变异和拷贝数变异（CNVs）在新诊断多发性骨髓瘤（NDMM）患者中的预后价值，进行了综合基因组分析。
本研究纳入了 67 例骨髓抽吸物中浆细胞比例超过 60%的 NDMM 患者。对骨髓有核细胞进行全外显子测序。使用 CNVkit 和 Nexus Copy Number 软件进行突变和 CNV 分析。此外，还进行了核型分析和荧光原位杂交分析。
在 63 例 NDMM 患者中检测到 83 个驱动基因突变。每位患者的突变中位数为 2.0（95%置信区间[CI] = 2.0-3.0，范围 0-8）。MAML2 和 BHLHE41 突变与生存时间缩短相关。在 56 例患者（72.7%；56/67）中检测到 CNVs。每位患者的 CNV 中位数为 6.0（95% CI = 5.7-7.0；范围 0-16）。在 CNVs 中，1q 增益、6p 增益、6q 缺失、8p 缺失和 13q 缺失与生存时间缩短相关。此外，1q 增益和 6p 增益是独立的不良预后因素。CNVs 和驱动基因突变数量的增加与不良临床结局相关。聚类分析显示，具有最高数量的驱动突变以及 1q 增益、6p 增益和 13q 缺失的患者预后最差。
除了已知的预后因素外，遗传变异和 CNVs 的综合分析有助于 NDMM 患者的预后分层。
