Neoplasia: An International Journal for Oncology Research (Feb 2025)

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

Journal volume & issue
Vol. 60
p. 101119

Abstract

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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.

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