Epstein-Barr virus infection shapes the genetic, transcriptomic, and immune microenvironment landscape of Burkitt lymphoma

Sep 30, 2026

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma whose occurrence and progression correlate with Epstein-Barr virus (EBV) status, yet molecular distinctions between EBV-positive and EBV-negative disease remain incompletely defined. Targeted sequencing of a 475-gene panel and RNA-seq/LncRNA-seq across BL cohorts identifies subtype-specific genomic alterations, transcriptional changes, and EBV-associated immune remodeling. EBV status is linked to distinct pathway enrichment and M1 macrophage infiltration with better 24-month overall survival, suggesting EBV-defined therapeutic vulnerabilities.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

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Abstract

Introduction

Burkitt lymphoma overview

Genetic alterations driving Burkitt lymphoma

Epstein-Barr virus and BL subtypes

Materials and methods (implied by sequencing and profiling)

Xiao et al. Infectious Agents and Cancer (2026) 21:4 Infectious Agents and Cancer [https://doi.org/10.1186/s13027-025-00720-9](https://doi.org/10.1186/s13027-025-00720-9) RESEARCH Open Access Epstein-Barr virus infection shapes the genetic, transcriptomic, and immune microenvironment landscape of Burkitt lymphoma Qing Xiao 1, Yilei Zhang 1, Zhongyi Chen 1, Xinrong Liu 1, Wentao Yu 1, Tiansheng Wang2 and Ling Chu 1* Abstract Burkitt lymphoma (BL) is a highly aggressive B-cell lymphoma with its occurrence and progression closely associated with Epstein-Barr virus (EBV) status. However, the molecular differences between EBV-positive and EBVnegative BL have not been comprehensively evaluated. Through targeted sequencing of a 475-gene panel in 27 BL cases, and RNA-seq and LncRNA-seq analyses of 25 cases, we found that EBV-negative tumors displayed a higher frequency of chromosomal amplifications, particularly at 7p12 . 2, 6q25 .3 and 7q22 .1. Two novel variants of KMT2D were identified in adult patients in the EBV-negative group. Furthermore, EBV-positive BL exhibited enriched FOXO1 mutations, in contrast to CCND3 hotspot variants in EBV-negative cases. Transcriptome profiling revealed 1,612 differential ly expressed genes (DEGs), predominantly involved in the PI3K-AKT, Hippo, WNT, and mTOR pathways. LncRNA profiling identified three EBV-associated lncRNAs ((MSTRG.103766. 1, MSTRG.33752. 11, ENSTO0000400385 . 2) with potential prognostic relevance in BL. Immune deconvolution (CIBERSORT/xCELL) demonstrated elevated M1 macrophages infiltration in EBV-positive BL, which correlated with improved 24-month overall survival (68% vs. 41%, p = 0 . 02) . SULT1C2P1 and KCNK5 emerged as M1-associated prognostic biomarkers. Our findings establish EBVas a key modulator of BL genomic instability and immune remodeling, leading us to hypothesize that EBV status defines distinct BL subtypes with unique therapeutic vulnerabilities, thereby enabling the future development of EBV-stratified precision therapies. Keywords Burkitt lymphoma, EBV, Gene alteration, Macrophage *Correspondence: Ling Chu[chu156@csu.edu.cn](chu156@csu.edu.cn) 1Department of Pathology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China 2Department of Otolaryngology, Head & Neck Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/. Xiao et al. Infectious Agents and Cancer (2026) 21:4 Introduction Burkitt lymphoma (BL) is a highly aggressive form of non-Hodgkin lymphoma (NHL), accounting for 3%-5% of all NHL cases. It is most common in children and young adults in China and frequently affects the jawbone, craniofacial bones, abdominal organs, and central nervous system [1]. A hallmark of BL is the extremely high proliferation rate of tumor cells, which has long been a research focus and a significant challenge in understanding its pathogenesis. Genetic alterations are fundamental to the development and specific biological functions of BL. BL was the first lymphoma described to harbor a recurren

FAQs

What is the study’s main goal regarding EBV status in Burkitt lymphoma?

To determine how molecular differences between EBV-positive and EBV-negative Burkitt lymphoma shape genomic, transcriptomic, and immune microenvironment features.

Which techniques were used to compare EBV-positive and EBV-negative tumors?

Targeted sequencing with a 475-gene panel, and RNA-seq and LncRNA-seq analyses, followed by immune deconvolution using CIBERSORT/xCELL.

How is the immune microenvironment different between EBV-positive and EBV-negative BL?

EBV-positive BL shows increased M1 macrophage infiltration, which correlates with improved 24-month overall survival.

Sep 30, 2026

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