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The Expanding Landscape of 'Oncohistone' Mutations in Human Cancers

The Expanding Landscape of 'Oncohistone' Mutations in Human Cancers

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

Nature. 2019 Mar;567(7749):473-478.

PMID: 30894748

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413478	Core Histones human			Price
IAR4246408	Histone H2B human			Price

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