The expanding landscape of ‘oncohistone’ mutations in human cancers

Benjamin A. Nacev, Lijuan Feng, John D. Bagert, Agata E. Lemiesz, Jian Jiong Gao, Alexey A. Soshnev, Ritika Kundra, Nikolaus Schultz, Tom W. Muir, C. David Allis

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)473-478
Number of pages6
JournalNature
Volume567
Issue number7749
DOIs
StatePublished - Mar 28 2019

All Science Journal Classification (ASJC) codes

  • General

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