Comparison of differences in transcriptional and genetic profiles between intra-central nervous system and extra-central nervous system large B-cell lymphoma

Comparison of differences in transcriptional and genetic profiles between intra-central nervous system and extra-central nervous system large B-cell lymphoma

Primary central nervous system diffused large B-cell lymphoma (PCNS-DLBCL) is a rare type of non-Hodgkin lymphoma restricted to the central nervous system (CNS). To explore its specific pathogenesis and therapeutic targets, we performed multi-omics sequencing on tumor samples from patients diagnosed...

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Main Authors: Shu Wang, Hong Chen, Bo Dai, Kang Zheng, Jiajun Zheng, Yuqi Zhu, Yan Yuan, Tianling Ding, Qian Wang, Liqian Xie, Rui Feng, Fengping Zhu, Jianbin Xiang, Weiqun Ding, Hong Ding, Yuan Li, Xiaodong Gu, Kunpeng Wu, Yifan Yuan, Jianping Song, Dongxiao Zhuang, Haoshu Zhong, Hanfeng Wu, Ying Mao, Tong Chen
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Neoplasia: An International Journal for Oncology Research
Subjects:
Diffuse large B cell lymphoma
Central nervous system
Single-cell RNA sequencing
Genomics
Tumor Microenvironment
Online Access:http://www.sciencedirect.com/science/article/pii/S147655862400160X
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Summary:Primary central nervous system diffused large B-cell lymphoma (PCNS-DLBCL) is a rare type of non-Hodgkin lymphoma restricted to the central nervous system (CNS). To explore its specific pathogenesis and therapeutic targets, we performed multi-omics sequencing on tumor samples from patients diagnosed with PCNS-DLBCL, secondary CNS-DLBCL or extracranial (ec) DLBCL.By single-cell RNA sequencing, highly proliferated and dark zone (DZ)-related B cell subclusters, MKI67_B1, PTTG1_B2 and BTG1_B3, were predominant significantly in PCNS-DLBCL. Compared to SCNS-DLBCL and ecDLBCL, an immune-suppressive tumor microenvironment was observed in PCNS-DLBCL by analysis of immune-stimulating/inhibitory ligand‒receptor (L-R) pairs. By performing whole-exome sequencing in 93 patients, mutations enriched in BCR-NFkB and TLR pathways and the cooperation of these two pathways were found to be predominant in PCNS-DLBCL comparing to nonGCB-ecDLBCL. In summary, our study provides comprehensive insights into the transcriptomic and genetic characteristics of PCNS-DLBCL in contrast to ecDLBCL and will help dissect the oncogenic mechanism of this disease.
ISSN:1476-5586

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