Histone Mutations in Cancer

Kosuke Funato; Viviane Tabar

doi:10.1146/annurev-cancerbio-030617-050143

Annual Review of Cancer Biology

Volume 2, 2018

Review Article

Free

Histone Mutations in Cancer

Kosuke Funato¹, and Viviane Tabar¹
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Affiliations: Center for Stem Cell Biology and Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; email: [email protected], [email protected]
Vol. 2:337-351 (Volume publication date March 2018) https://doi.org/10.1146/annurev-cancerbio-030617-050143
First published as a Review in Advance on December 01, 2017
© Annual Reviews

Abstract

Recurrent driver mutations in the genes encoding histones have been recently described in pediatric brain tumors, as well as in chondroblastomas and giant cell tumors of the bone. The mutations are often heterozygous and frequently comprise single amino acid substitutions in the tails of histone variants. Substitutions of methionine to lysine on H3.3K27 or H3.3K36 are the most common alterations, occurring in diffuse intrinsic pontine gliomas (DIPGs) and chondroblastomas, respectively. Current data suggest that histone mutations alter the epigenetic landscape in tumor cells and lead to a blockade of differentiation, but the mechanisms underlying oncogenesis are not fully understood. These mutations also exhibit a propensity for exclusive expression in specific cell lineages and, in the case of brain tumors, a remarkable anatomic and developmental specificity. The histone mutations have raised interest in promising novel therapeutic strategies that incorporate epigenetic drugs.

Keyword(s): cancer epigenetics, diffuse glioma, DIPG, histone mutations, pediatric cancers

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2018-03-04

2024-04-24

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