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

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

doi:10.1016/j.neo.2024.101119

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

Neoplasia. 2024 Dec 28:60:101119. doi: 10.1016/j.neo.2024.101119. Online ahead of print.

Authors

Shu Wang¹, Hong Chen², Bo Dai¹, Kang Zheng³, Jiajun Zheng³, Yuqi Zhu⁴, Yan Yuan¹, Tianling Ding¹, Qian Wang¹, Liqian Xie³, Rui Feng⁵, Fengping Zhu³, Jianbin Xiang⁶, Weiqun Ding⁷, Hong Ding⁸, Yuan Li⁴, Xiaodong Gu⁹, Kunpeng Wu¹, Yifan Yuan¹⁰, Jianping Song¹¹, Dongxiao Zhuang³, Haoshu Zhong¹, Hanfeng Wu¹², Ying Mao¹³, Tong Chen¹⁴

Affiliations

¹ Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
² Department of Pathology, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
³ Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
⁴ Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
⁵ Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, PR China; National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai 200040, PR China; Neurosurgical Institute of Fudan University, Huashan Hospital, Shanghai 200040, PR China.
⁶ Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
⁷ Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
⁸ Department of Ultrasound, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
⁹ Department of Gastrointestinal Surgery, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
¹⁰ Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, PR China; National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
¹¹ Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, PR China; National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai 200040, PR China; Neurosurgical Institute of Fudan University, Huashan Hospital, Shanghai 200040, PR China; Shanghai Clinical Medical Center of Neurosurgery, Shanghai 200040, PR China; Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai 200040, PR China.
¹² Department of Neurosurgery, Shanghai Gamma Hospital, Shanghai 200235, PR China. Electronic address: wolf2yy@qq.com.
¹³ Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, PR China. Electronic address: maoying@fudan.edu.cn.
¹⁴ Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, PR China. Electronic address: chentong@fudan.edu.cn.

PMID: 39733690
DOI: 10.1016/j.neo.2024.101119

Abstract

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.

Keywords: Central nervous system; Diffuse large B cell lymphoma; Genomics; Single-cell RNA sequencing; Tumor Microenvironment.