期刊
CANCERS
卷 14, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/cancers14051284
关键词
Burkitt lymphoma; EBV; AFB1; DNA methylation
类别
资金
- La Ligue Contre le Cancer (LNCC) Rhone [GR-IARC-2014-04-07-03, OPE-2017-0009]
- Oncostarter-(CLARA) [GR-IARC-2014-05-15-02]
- Plan Cancer-INSERM [17CE032-00]
- FWO Belgium [G085921N]
- Fondation ARC pour la Recherche sur le Cancer [ARCDOC42021020003117]
- MSCA-IF [VirGO 896422]
- Children with Cancer UK (CwC UK) [PP201910-33]
- Bill and Melinda Gates Foundation [OPP1061062]
- PEDIAC origines des cancers pediatriques grant from the national cancer institute (INCA France) [INCA_15670]
- IARC Junior Award 2016 (AFEES-2016)
- [AFEES-2016]
- [896422]
- Bill and Melinda Gates Foundation [OPP1061062] Funding Source: Bill and Melinda Gates Foundation
Endemic Burkitt lymphoma is a pediatric cancer caused by EBV infection, malaria, and environmental carcinogens. This study identified a common molecular signature associated with both EBV and AFB1 exposure, which may play a crucial role in the development of lymphoma.
Simple Summary Endemic Burkitt lymphoma is an aggressive pediatric cancer whose etiological factors include Epstein-Barr virus (EBV) infection and malaria or environmental carcinogen exposures, such as aflatoxin B1 (AFB1). As evidence suggests B cell methylome remodeling to be a transformation mechanism shared by both EBV and AFB1, the identification of a common molecular signature compromising cell fate could reveal an essential driver of lymphomagenesis and provide a relevant target for novel therapies. We, therefore, explored the genome-wide DNA methylation profiles associated with both endemic Burkitt lymphoma and AFB1 exposure and identified a shared signature affecting the expression of a putative tumor suppressor, TGFBI, whose reduced expression has already been investigated in several cancers, but whose implication in lymphoma has not been evidenced so far. Further research clarifying the functional consequence of TGFBI suppression on B cell fate and the impact on tumor microenvironment reshaping is warranted. Burkitt lymphoma (BL) is a malignant B cell neoplasm that accounts for almost half of pediatric cancers in sub-Saharan African countries. Although the BL endemic prevalence is attributable to the combination of Epstein-Barr virus (EBV) infection with malaria and environmental carcinogens exposure, such as the food contaminant aflatoxin B1 (AFB1), the molecular determinants underlying the pathogenesis are not fully understood. Consistent with the role of epigenetic mechanisms at the interface between the genome and environment, AFB1 and EBV impact the methylome of respectively leukocytes and B cells specifically. Here, we conducted a thorough investigation of common epigenomic changes following EBV or AFB1 exposure in B cells. Genome-wide DNA methylation profiling identified an EBV-AFB1 common signature within the TGFBI locus, which encodes for a putative tumor suppressor often altered in cancer. Subsequent mechanistic analyses confirmed a DNA-methylation-dependent transcriptional silencing of TGFBI involving the recruitment of DNMT1 methyltransferase that is associated with an activation of the NF-kappa B pathway. Our results reveal a potential common mechanism of B cell transformation shared by the main risk factors of endemic BL (EBV and AFB1), suggesting a key determinant of disease that could allow the development of more efficient targeted therapeutic strategies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据