Yuan Xianggui, Yu Teng, Zhao Jianzhi, Jiang Huawei, Hao Yuanyuan, Lei Wen, Liang Yun, Li Baizhou, Qian Wenbin
Department of Hematology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
Department of Pathology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
Front Med. 2023 Oct;17(5):889-906. doi: 10.1007/s11684-023-0994-x. Epub 2023 Jul 7.
Primary central nervous system lymphoma (PCNSL) is an uncommon non-Hodgkin's lymphoma with poor prognosis. This study aimed to depict the genetic landscape of Chinese PCNSLs. Whole-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples, whose genomic characteristics and clinicopathologic features were also analyzed. Structural variations were identified in all patients with a mean of 349, which did not significantly influence prognosis. Copy loss occurred in all samples, while gains were detected in 77.9% of the samples. The high level of copy number variations was significantly associated with poor progression-free survival (PFS) and overall survival (OS). A total of 263 genes mutated in coding regions were identified, including 6 newly discovered genes (ROBO2, KMT2C, CXCR4, MYOM2, BCLAF1, and NRXN3) detected in ⩾ 10% of the cases. CD79B mutation was significantly associated with lower PFS, TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS. A prognostic risk scoring system was also established for PCNSL, which included Karnofsky performance status and six mutated genes (BRD4, EBF1, BTG1, CCND3, STAG2, and TMSB4X). Collectively, this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs, thereby enriching the present understanding of the genetic mechanisms of PCNSL.
原发性中枢神经系统淋巴瘤（PCNSL）是一种预后较差的罕见非霍奇金淋巴瘤。本研究旨在描绘中国PCNSL的基因图谱。对68例新诊断的中国PCNSL样本进行了全基因组测序，并分析了其基因组特征和临床病理特征。所有患者均检测到结构变异，平均变异数为349个，这些变异对预后无显著影响。所有样本均出现拷贝数缺失，而77.9%的样本检测到拷贝数增加。高水平的拷贝数变异与无进展生存期（PFS）和总生存期（OS）较差显著相关。共鉴定出263个编码区突变基因，包括6个新发现的基因（ROBO2、KMT2C、CXCR4、MYOM2、BCLAF1和NRXN3），在≥10%的病例中检测到。CD79B突变与较低的PFS显著相关，TMSB4X突变和TMSB4X蛋白高表达与较低的OS相关。还建立了PCNSL的预后风险评分系统，该系统包括卡诺夫斯基功能状态和6个突变基因（BRD4、EBF1、BTG1、CCND3、STAG2和TMSB4X）。总体而言，本研究全面揭示了新诊断的中国PCNSL的基因组图谱，从而丰富了目前对PCNSL遗传机制的认识。
