Histone H3 Mutations in Cancer

被引：39

作者：

Wan Y.C.E. ^{[1
,2
]}

Liu J. ^{[1
,2
]}

Chan K.M. ^{[1
,2
]}

机构：

[1] Department of Biomedical Sciences, City University of Hong Kong

[2] Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen

来源：

Current Pharmacology Reports | 2018年 / 4卷 / 4期

关键词：

Cancer; H3K27M; H3K36M; Histone mutations;

D O I：

10.1007/s40495-018-0141-6

中图分类号：

学科分类号：

摘要：

Histone modifications are one form of epigenetic information that relate closely to gene regulation. Aberrant histone methylation caused by alteration in chromatin-modifying enzymes has long been implicated in cancers. More recently, recurrent histone mutations have been identified in multiple cancers and have been shown to impede histone methylation. All three histone mutations (H3K27M, H3K36M, and H3G34V/R) identified result in amino acid substitution at/near a lysine residue that is a target of methylation. In the cases of H3K27M and H3K36M, found in pediatric DIPG (diffuse intrinsic pontine glioma) and chondroblastoma respectively, expression of the mutant histone leads to global reduction of histone methylation at the respective lysine residue. These mutant histones are termed “oncohistones” because their expression reprograms the epigenome and shapes an oncogenic transcriptome. Dissecting the mechanism of H3K27M-driven oncogenesis has led to the discovery of promising therapeutic targets in pediatric DIPG. The purpose of this review is to summarize the work done on identifying and dissecting the oncogenic properties of histone H3 mutations. © 2018, The Author(s).

引用

页码：292 / 300

页数：8

共 52 条

[1]

Tagami H., Ray-Gallet D., Almouzni G., Nakatani Y., Histone H3.1 and H3.3 Complexes Mediate Nucleosome Assembly Pathways Dependent or Independent of DNA Synthesis, Cell, 116, 1, pp. 51-61, (2004)

[2]

Goldberg A.D., Banaszynski L.A., Noh K.M., Lewis P.W., Elsaesser S.J., Stadler S., Et al., Distinct Factors Control Histone Variant H3.3 Localization at Specific Genomic Regions, Cell, 140, 5, pp. 678-691, (2010)

[3]

Jones C., Perryman L., Hargrave D., Paediatric and adult malignant glioma: Close relatives or distant cousins?, Nat Rev Clin Oncol, 9, 7, pp. 400-413, (2012)

[4]

Schwartzentruber J., Korshunov A., Liu X.-Y., Jones D.T.W., Pfaff E., Jacob K., Et al., Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma, Nature, 482, 7384, pp. 226-231, (2012)

[5]

Sturm D., Witt H., Hovestadt V., Khuong-Quang D.-A., Jones D.T.W., Konermann C., Et al., Hotspot Mutations in H3F3A and IDH1 Define Distinct Epigenetic and Biological Subgroups of Glioblastoma, Cancer Cell, 22, 4, pp. 425-437, (2012)

[6]

Wu G., Broniscer A., McEachron T.A., Lu C., Paugh B.S., Becksfort J., Et al., Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas, Nat Genet, 44, 3, pp. 251-253, (2012)

[7]

Castel D., Philippe C., Calmon R., Le Dret L., Truffaux N., Boddaert N., Et al., Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes, Acta Neuropathol, 130, 6, pp. 815-827, (2015)

[8]

Fontebasso A.M., Papillon-Cavanagh S., Schwartzentruber J., Nikbakht H., Gerges N., Fiset P.O., Et al., Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma, Nat Genet, 46, 5, pp. 462-466, (2014)

[9]

Mackay A., Burford A., Carvalho D., Izquierdo E., Fazal-Salom J., Taylor K.R., Et al., Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma, Cancer Cell, 32, 4, pp. 520-537, (2017)

[10]

Taylor K.R., Mackay A., Truffaux N., Butterfield Y.S., Morozova O., Philippe C., Et al., Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma, Nat Genet, 46, 5, pp. 457-461, (2014)

← 1 2 3 4 5 6 →