DNA methylation epitypes of Burkitt lymphoma with distinct molecular and clinical features.

IF 11.5 Q1 HEMATOLOGY

Blood Cancer Discovery Pub Date : 2025-05-08 DOI:10.1158/2643-3230.BCD-24-0240

Nicole Thomas, Carlos A García-Prieto, Kostiantyn Dreval, Laura K Hilton, Jeremy S Abramson, Nancy L Bartlett, Jeffrey Bethony, Jay Bowen, Anthony C Bryan, Corey Casper, Maureen A Dyer, Julie M Gastier-Foster, Alina S Gerrie, Timothy C Greiner, Nicholas B Griner, Thomas G Gross, Nancy Harris, John D Irvin, Elaine S Jaffe, Fabio E Leal, Sam M Mbulaiteye, Charles G Mullighan, Andrew J Mungall, Karen L Mungall, Constance Namirembe, Ariela Noy, Martin D Ogwang, Jackson Orem, German Ott, Hilary Petrello, Steven J Reynolds, Steven H Swerdlow, Alexandra Traverse-Glehen, Wyndham H Wilson, Marco A Marra, Louis M Staudt, David W Scott, Manel Esteller, Ryan D Morin

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Abstract

The genetic subtypes of Burkitt Lymphoma (BL) have been defined, whereas the role of epigenetics remains to be comprehensively characterized. We searched genomic DNA from 218 patients across four continents, for recurrent DNA methylation patterns and their associations with clinical and molecular features. We identified DNA methylation patterns that were not fully explained by EBV status or mutation status, leading to two epitypes, described here as HypoBL and HyperBL. Each is characterized by distinct genomic and clinical features including global methylation, mutation burden, aberrant somatic hypermutation, and survival outcomes. Methylation, gene expression and mutational differences between the epitypes support a model in which each arises from a distinct cell-of-origin. These results, pending validation in external cohorts, point to a refined risk assessment for BL patients who may experience inferior outcomes.

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具有不同分子和临床特征的伯基特淋巴瘤的DNA甲基化亚型。

伯基特淋巴瘤（BL）的遗传亚型已经确定，而表观遗传学的作用仍有待全面表征。我们检索了来自四大洲的218名患者的基因组DNA，以寻找复发性DNA甲基化模式及其与临床和分子特征的关联。我们发现DNA甲基化模式不能完全解释EBV状态或突变状态，导致两种表型，这里描述为HypoBL和HyperBL。每一种都有不同的基因组和临床特征，包括整体甲基化、突变负担、异常体细胞超突变和生存结果。甲基化、基因表达和表型之间的突变差异支持一个模型，其中每个表型都来自不同的细胞起源。这些结果有待外部队列的验证，指出了可能经历不良结果的BL患者的精确风险评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Blood Cancer Discovery Multiple-

CiteScore

12.70

自引率

1.80%

发文量

139

期刊介绍： The journal Blood Cancer Discovery publishes high-quality Research Articles and Briefs that focus on major advances in basic, translational, and clinical research of leukemia, lymphoma, myeloma, and associated diseases. The topics covered include molecular and cellular features of pathogenesis, therapy response and relapse, transcriptional circuits, stem cells, differentiation, microenvironment, metabolism, immunity, mutagenesis, and clonal evolution. These subjects are investigated in both animal disease models and high-dimensional clinical data landscapes. The journal also welcomes submissions on new pharmacological, biological, and living cell therapies, as well as new diagnostic tools. They are interested in prognostic, diagnostic, and pharmacodynamic biomarkers, and computational and machine learning approaches to personalized medicine. The scope of submissions ranges from preclinical proof of concept to clinical trials and real-world evidence. Blood Cancer Discovery serves as a forum for diverse ideas that shape future research directions in hematooncology. In addition to Research Articles and Briefs, the journal also publishes Reviews, Perspectives, and Commentaries on topics of broad interest in the field.