TY  - JOUR
AU  - Salomoni, Paolo
AU  - Flanagan, Adrienne M.
AU  - Cottone, Lucia
TI  - (B)On(e)-cohistones and the epigenetic alterations at the root of bone cancer
JO  - Cell death and differentiation
VL  - 32
IS  - 1
SN  - 1350-9047
CY  - London
PB  - Macmillan
M1  - DZNE-2023-01164
SP  - 66 - 77
PY  - 2025
AB  - Identification of mutations in histones in a number of human neoplasms and developmental syndromes represents the most compelling evidence to date for a causal role of epigenetic perturbations in human disease. In most cases, these mutations have gain of function properties that cause deviation from normal developmental processes leading to embryo defects and/or neoplastic transformation. These exciting discoveries represent a step-change in our understanding of the role of chromatin (dys)regulation in development and disease. However, the mechanisms of action of oncogenic histone mutations (oncohistones) remain only partially understood. Here, we critically assess existing literature on oncohistones focussing mainly on bone neoplasms. We show how it is possible to draw parallels with some of the cell-autonomous mechanisms of action described in paediatric brain cancer, although the functions of oncohistones in bone tumours remain under-investigated. In this respect, it is becoming clear that histone mutations targeting the same residues display, at least in part, tissue-specific oncogenic mechanisms. Furthermore, it is emerging that cancer cells carrying oncohistones can modify the surrounding microenvironment to support growth and/or alter differentiation trajectories. A better understanding of oncohistone function in different neoplasms provide potential for identification of signalling that could be targeted therapeutically. Finally, we discuss some of the main concepts and future directions in this research area, while also drawing possible connections and parallels with other cancer epigenetic mechanisms.
KW  - Humans
KW  - Epigenesis, Genetic
KW  - Bone Neoplasms: genetics
KW  - Bone Neoplasms: metabolism
KW  - Bone Neoplasms: pathology
KW  - Histones: metabolism
KW  - Mutation
KW  - Animals
LB  - PUB:(DE-HGF)16
C6  - pmid:37828086
C2  - pmc:PMC11748643
DO  - DOI:10.1038/s41418-023-01227-9
UR  - https://pub.dzne.de/record/266479
ER  -