Neurosurgery, China International Neuroscience Institute, Xuanwu Hospital Capital Medical University, Beijing, China.
Genetron Health (Beijing) Co. Ltd., Beijing, China.
Medicine (Baltimore). 2023 Sep 1;102(35):e34931. doi: 10.1097/MD.0000000000034931.
Primary central nervous system lymphoma (PCNSL) is a rare and special type of non-Hodgkin lymphoma with a significantly worse median overall prognosis than that of non-Hodgkin lymphoma outside the brain. Clarifying the genomic characteristics and alterations in PCNSL could provide clues regarding its distinctive pathophysiology and new treatment options. However, current knowledge about the genomics of PCNSL is limited. In this study, next-generation sequencing (NGS) was performed to investigate the genomic profile of PCNSL. Samples from 12 patients diagnosed with PCNSL at our institution were analyzed for gene mutations using NGS. This study showed that missense mutations were the most common mutation type. C > A/G > T accounted for most of the single-base mutations, which reflected the preference of the tumor sample mutation type and may serve as an important prognostic factor. The most significantly mutated gene was myeloid differentiation factor 88 (MYD88) (0.55), followed by CD79B, LRP1B, and PRDM1 (0.36). None of the cases showed a high tumor mutational burden. In addition to the traditional driver genes, we also identified some new possible ones such as MET, PIM1, and RSBN1L. Enrichment analysis revealed that genes mutated in PCNSL were involved in many pathways and functional protein activities, such as the extracellular matrix and adhesion molecules. The most common genetic alterations in PCNSL were identified using NGS. Mutations in multiple genes highlights the complex molecular heterogeneity of PCNSL. Enrichment analysis revealed possible pathogenesis. Further exploration of new driver genes could provide novel insights into diagnosis and precision medicine for PCNSL.
原发性中枢神经系统淋巴瘤（PCNSL）是一种罕见且特殊类型的非霍奇金淋巴瘤，其总体预后明显较脑外非霍奇金淋巴瘤差。阐明 PCNSL 的基因组特征和改变可为其独特的病理生理学提供线索，并为新的治疗选择提供依据。然而，目前对 PCNSL 的基因组学知识有限。在本研究中，我们采用下一代测序（NGS）来研究 PCNSL 的基因组特征。对本机构诊断为 PCNSL 的 12 例患者的样本进行 NGS 基因检测，分析基因突变情况。该研究显示，错义突变是最常见的突变类型。C > A/G > T 占多数碱基突变，反映了肿瘤样本突变类型的偏好，可能是一个重要的预后因素。突变频率最高的基因是髓样分化因子 88（MYD88）（0.55），其次是 CD79B、LRP1B 和 PRDM1（0.36）。所有病例均未显示高肿瘤突变负担。除了传统的驱动基因外，我们还鉴定出一些新的潜在驱动基因，如 MET、PIM1 和 RSBN1L。富集分析显示，PCNSL 中突变的基因涉及许多途径和功能蛋白活性，如细胞外基质和黏附分子。本研究通过 NGS 鉴定出了 PCNSL 中最常见的遗传改变。多个基因的突变突出了 PCNSL 复杂的分子异质性。富集分析揭示了可能的发病机制。进一步探索新的驱动基因可能为 PCNSL 的诊断和精准医学提供新的见解。
