@article{3562,
  keywords = {Humans, Mutation, Protein Processing, Post-Translational, Methylation, Cell Transformation, Neoplastic, Histones, Nucleosomes, Neoplasms, Lysine, Protein Domains},
  author = {Benjamin Nacev and Lijuan Feng and John Bagert and Agata Lemiesz and JianJiong Gao and Alexey Soshnev and Ritika Kundra and Nikolaus Schultz and Tom Muir and C David Allis},
  title = {The expanding landscape of {\textquoteright}oncohistone{\textquoteright} mutations in human cancers.},
  abstract = { <p>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 {\textquoteright}oncohistone{\textquoteright} 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 {\textquoteright}acidic patch{\textquoteright} 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.</p> },
  year = {2019},
  journal = {Nature},
  volume = {567},
  pages = {473-478},
  month = {2019 Mar},
  issn = {1476-4687},
  doi = {10.1038/s41586-019-1038-1},
  language = {eng},
}