The expanding landscape of ‘oncohistone’ mutations in human cancers Journal Article

Authors: Nacev, B. A.; Feng, L.; Bagert, J. D.; Lemiesz, A. E.; Gao, J.; Soshnev, A. A.; Kundra, R.; Schultz, N.; Muir, T. W.; Allis, C. D.
Article Title: The expanding landscape of ‘oncohistone’ mutations in human cancers
Abstract: Mutations in epigenetic pathways are common oncogenic drivers. Histones, the fundamental substrates for chromatin-modifying and remodelling enzymes, are mutated in tumours including gliomas, sarcomas, head and neck cancers, and carcinosarcomas. Classical ‘oncohistone’ mutations occur in the N-terminal tail of histone H3 and affect the function of polycomb repressor complexes 1 and 2 (PRC1 and PRC2). However, the prevalence and function of histone mutations in other tumour contexts is unknown. Here we show that somatic histone mutations occur in approximately 4% (at a conservative estimate) of diverse tumour types and in crucial regions of histone proteins. Mutations occur in all four core histones, in both the N-terminal tails and globular histone fold domains, and at or near residues that contain important post-translational modifications. Many globular domain mutations are homologous to yeast mutants that abrogate the need for SWI/SNF function, occur in the key regulatory ‘acidic patch’ of histones H2A and H2B, or are predicted to disrupt the H2B–H4 interface. The histone mutation dataset and the hypotheses presented here on the effect of the mutations on important chromatin functions should serve as a resource and starting point for the chromatin and cancer biology fields in exploring an expanding role of histone mutations in cancer. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.
Keywords: mutation; protein; enzyme activity; tumor; pigment; exploration; cancer; landscape change
Journal Title: Nature
Volume: 567
Issue: 7749
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2019-03-28
Start Page: 473
End Page: 478
Language: English
DOI: 10.1038/s41586-019-1038-1
PUBMED: 30894748
PROVIDER: scopus
PMCID: PMC6512987
Notes: Source: Scopus
Citation Impact
MSK Authors
  1. Jianjiong Gao
    83 Gao
  2. Nikolaus D Schultz
    283 Schultz
  3. Ritika   Kundra
    36 Kundra
  4. Benjamin Alexander Nacev
    4 Nacev
  5. C. David Allis
    1 Allis