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REVIEW article

Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1455572
This article is part of the Research Topic Cancer Pathogenesis: Molecular and Cellular Mechanisms of Tumor evolution, Therapy-Resistance and Immune Evasion View all 9 articles

The emerging role of cancer-associated histone mutations in genomic instability

Provisionally accepted
Priyanka Yadav Priyanka Yadav Ronit Jain Ronit Jain Rajesh Kumar Yadav Rajesh Kumar Yadav *
  • National Institute of Immunology (NII), New Delhi, India

The final, formatted version of the article will be published soon.

    Epigenetic mechanisms fuel the quick evolution of cancer cells from normal cells. Mutations or aberrant expressions in the enzymes of DNA methylation, histone posttranslational modifications and chromatin remodelers are well investigated in cancer pathogenesis, however, cancerassociated histone mutants have gained momentum in the recent decade. Next-generation sequencing of cancer cells has identified somatic recurrent mutations in all the histones (H3, H4, H2A, H2B and H1) with various frequencies in various tumour types. Importantly, wellcharacterized H3K27M, H3G34R/V, and H3K36M mutations are termed as onco-histone mutants because of their wide role from the defect in cellular differentiation, transcriptional dysregulation, perturbed epigenomic profiles to genomic instability. Mechanistically, these histone mutants impart their effect on histone modifications and/or on irregular distribution of chromatin complexes. Recent studies identify the crucial role of H3K27M and H3G34R/V mutants in the DNA Damage Response (DDR) pathway but their impact on chemotherapy and tumour progression remains elusive. In this review, we have summarized the new developments in their function toward genomic instability and tumour progression. Finally, how this mechanistic understanding can be harnessed toward the potential treatment for tumours harbouring H3K27M, H3G34R/V, and H3K36M mutation.

    Keywords: min 5, max 8): Chromatin, Genomic Instability, oncohistone, Epigenetic mechanisms, histone mutations, Central Nervous System, oncology

    Received: 27 Jun 2024; Accepted: 10 Sep 2024.

    Copyright: © 2024 Yadav, Jain and Yadav. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Rajesh Kumar Yadav, National Institute of Immunology (NII), New Delhi, India

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.