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.

中文翻译：

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淋巴肿瘤的表观基因组学特征


淋巴肿瘤代表了一组异质性的疾病实体和亚型，具有显著不同的分子和临床特征。除了基因改变外，淋巴瘤还表现出广泛的表观基因组变化。这些会严重影响 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 甲基化作为细胞身份和记忆的示踪剂脱颖而出，因为 B 细胞肿瘤显示出其细胞起源和增殖历史的表观遗传印记，这可以通过表观遗传有丝分裂时钟进行量化。染色质相关标记有助于揭示导致不同淋巴肿瘤发展的改变的调节区域和转录因子网络。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，以在淋巴瘤进化的不同阶段塑造转录组，并且克隆内异质性现在可以通过单细胞分析来表征。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。