Epigenomic Characterization of Lymphoid Neoplasms.

IF 28.4 1区医学 Q1 PATHOLOGY Annual Review of Pathology-Mechanisms of Disease Pub Date : 2024-01-24 Epub Date: 2023-10-13 DOI:10.1146/annurev-pathmechdis-051122-100856

Martí Duran-Ferrer, José Ignacio Martín-Subero

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Abstract

Lymphoid neoplasms represent a heterogeneous group of disease entities and subtypes with markedly different molecular and clinical features. Beyond genetic alterations, lymphoid tumors also show widespread epigenomic changes. These severely affect the levels and distribution of DNA methylation, histone modifications, chromatin accessibility, and three-dimensional genome interactions. DNA methylation stands out as a tracer of cell identity and memory, as B cell neoplasms show epigenetic imprints of their cellular origin and proliferative history, which can be quantified by an epigenetic mitotic clock. Chromatin-associated marks are informative to uncover altered regulatory regions and transcription factor networks contributing to the development of distinct lymphoid tumors. Tumor-intrinsic epigenetic and genetic aberrations cooperate and interact with microenvironmental cells to shape the transcriptome at different phases of lymphoma evolution, and intraclonal heterogeneity can now be characterized by single-cell profiling. Finally, epigenetics offers multiple clinical applications, including powerful diagnostic and prognostic biomarkers as well as therapeutic targets.

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淋巴肿瘤的表观基因组特征。

淋巴肿瘤代表了一组具有明显不同分子和临床特征的异质性疾病实体和亚型。除了基因改变外，淋巴肿瘤还表现出广泛的表观基因组变化。这些严重影响DNA甲基化、组蛋白修饰、染色质可及性和三维基因组相互作用的水平和分布。DNA甲基化是细胞身份和记忆的示踪剂，因为B细胞肿瘤显示出其细胞起源和增殖史的表观遗传印记，这可以通过表观遗传有丝分裂时钟来量化。染色质相关标记有助于揭示导致不同淋巴肿瘤发展的调节区和转录因子网络的改变。肿瘤内在的表观遗传和遗传畸变与微环境细胞合作并相互作用，在淋巴瘤进化的不同阶段形成转录组，现在可以通过单细胞图谱来表征克隆内的异质性。最后，表观遗传学提供了多种临床应用，包括强大的诊断和预后生物标志物以及治疗靶点。《病理学年度评论：疾病机制》第19卷预计最终在线出版日期为2024年1月。请参阅http://www.annualreviews.org/page/journal/pubdates用于修订估算。

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

Annual Review of Pathology-Mechanisms of Disease 医学-病理学

CiteScore

62.60

自引率

0.00%

发文量

期刊介绍： The Annual Review of Pathology: Mechanisms of Disease is a scholarly journal that has been published since 2006. Its primary focus is to provide a comprehensive overview of recent advancements in our knowledge of the causes and development of significant human diseases. The journal places particular emphasis on exploring the current and evolving concepts of disease pathogenesis, as well as the molecular genetic and morphological changes associated with various diseases. Additionally, the journal addresses the clinical significance of these findings. In order to increase accessibility and promote the broad dissemination of research, the current volume of the journal has transitioned from a gated subscription model to an open access format. This change has been made possible through the Annual Reviews' Subscribe to Open program, which allows all articles published in this volume to be freely accessible to readers. As part of this transition, all articles in the journal are published under a Creative Commons Attribution (CC BY) license, which encourages open sharing and use of the research.