Analysis of the genomic landscape of primary central nervous system lymphoma using whole-genome sequencing in Chinese patients

Abstract

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.

Keywords

primary central nervous system lymphoma / whole-genome sequencing / TMSB4X / copy number variation / gene mutation

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Acknowledgments

We thank Shanghai Yuanqi Biomedical Technology Co. Ltd. (Shanghai, China) for the bioinformatics analysis. This study was supported by funds from the Translational Research Grant of National Clinical Research Center for Hematologic Disease (No. 2020ZKZC01), the National Natural Science Foundation of China (Nos. 81830006, 82170219, and 81800188) and the Lymphoma Research Fund of China Anti-Cancer Association.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-023-0994-x and is accessible for authorized users.

Compliance with ethics guidelines

Xianggui Yuan, Teng Yu, Jianzhi Zhao, Huawei Jiang, Yuanyuan Hao, Wen Lei, Yun Liang, Baizhou Li, and Wenbin Qian declare that they have no conflict of interest. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

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