原发性中枢神经系统淋巴瘤（PCNSL）是一种罕见且特殊的非霍奇金淋巴瘤，其中位总体预后明显差于脑外非霍奇金淋巴瘤。阐明PCNSL的基因组特征和改变可能提供关于其独特病理生理学和新治疗选择的线索。然而，目前对PCNSL基因组的了解有限。本研究采用下一代测序（NGS）技术对PCNSL的基因组进行了调查。分析了本院收治的12例PCNSL患者样本，使用NGS检测基因突变。研究表明，错义突变是最常见的突变类型。单碱基突变中，C > A/G > T占据了大部分，反映了肿瘤样本突变类型的偏好，可能作为一种重要的预后因素。最显著的突变基因是髓系分化因子88（MYD88）（0.55），其次是CD79B，LRP1B和PRDM1（0.36）。没有一个样本显示出高肿瘤突变负荷。除了传统的驱动基因外，我们还发现了一些可能的新驱动基因，如MET，PIM1和RSBN1L。富集分析显示PCNSL中发生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。利用NGS技术鉴定了PCNSL中最常见的遗传变异。多基因突变突显了PCNSL的复杂分子异质性。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。 版权 © 2023 作者。Wolters Kluwer Health, Inc.发表。

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.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.