Zhu Qiong, Wang Jianchao, Zhang Wenfang, Zhu Weifeng, Wu Zaizeng, Chen Yanping, Chen Musheng, Zheng Limei, Tang Jianqing, Zhang Sheng, Wang Di, Wang Xingfu, Chen Gang
Department of Molecular Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China.
Department of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China.
Front Genet. 2022 May 12;13:878618. doi: 10.3389/fgene.2022.878618. eCollection 2022.
Identification of key genetic alterations is of importance in the targeted therapies of primary central nervous system lymphoma (PCNSL). However, only a small number of studies have been carried out in PCNSL. In this study, we further described the genetic mutations and copy number variations (CNVs) in PCNSL patients using whole-genome/exome sequencing (WGS/WES), as well as revealed their associations with patients' clinicopathological features and prognosis. Tumor specimens from 38 patients with primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) were enrolled to WGS ( = 24) or WES ( = 14). The CNVs and mutations of 24 samples (WGS) and 38 samples (WGS/WES) were characterized, respectively. The associations between CNVs and mutations with the overall survival rates of PCNSL patients were also evaluated. The most common mutations were identified in (68%), (63%), (55%), (42%), (39%), (39%), (34%), and (29%) genes. Among the mutated genes, , and mutations were exclusively detected in the elderly, while mutations were associated with the immune microenvironment indicators. In addition, mutation was associated with a poor prognosis. In addition, 488 CNVs including 91 gains and 397 deletions were observed across 24 samples from WGS results. Notably, 1q31.3 amplification was closely associated with the poor prognosis of PCNSL patients. This study further characterizes the genomic landscape of primary CNS DLBCL using WGS/WES, which provides insight into understanding the pathogenesis of PCNSL and fosters new ideas for the targeted treatment of PCNSL.
识别关键基因改变在原发性中枢神经系统淋巴瘤（PCNSL）的靶向治疗中具有重要意义。然而，针对PCNSL的研究较少。在本研究中，我们使用全基因组/外显子组测序（WGS/WES）进一步描述了PCNSL患者的基因突变和拷贝数变异（CNV），并揭示了它们与患者临床病理特征和预后的关系。纳入38例原发性中枢神经系统弥漫性大B细胞淋巴瘤（CNS DLBCL）患者的肿瘤标本进行WGS（n = 24）或WES（n = 14）。分别对24个样本（WGS）和38个样本（WGS/WES）的CNV和突变进行了特征分析。还评估了CNV和突变与PCNSL患者总生存率之间的关联。最常见的突变发生在TP53（68%）、CD79B（63%）、MYD88（55%）、BCL2（42%）、MLL2（39%）、KMT2D（39%）、PRDM1（34%）和CREBBP（29%）基因中。在突变基因中，TP53、CD79B和MYD88突变仅在老年患者中检测到，而BCL2突变与免疫微环境指标相关。此外，MYD88突变与预后不良相关。此外，根据WGS结果，在24个样本中观察到488个CNV，包括91个增益和397个缺失。值得注意的是，1q31.3扩增与PCNSL患者的不良预后密切相关。本研究使用WGS/WES进一步描绘了原发性中枢神经系统DLBCL的基因组图谱，为理解PCNSL的发病机制提供了见解，并为PCNSL的靶向治疗提出了新思路。
