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Epigenomic Characterization of Lymphoid Neoplasms

Authors
  • Duran-Ferrer, Martí
  • Martín-Subero, José Ignacio
Type
Published Article
Journal
Annual Review of Pathology Mechanisms of Disease
Publisher
Annual Reviews
Publication Date
Jan 24, 2024
Volume
19
Pages
371–396
Identifiers
DOI: 10.1146/annurev-pathmechdis-051122-100856
Source
Annual Reviews
Keywords
License
Green

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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