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Histone H3.3K27M mobilizes multiple cancer/testis (CT) antigens in pediatric glioma
Deng H.2; Zeng J.2; Zhang T.2; Gong L.2; Zhang H.2; Cheung E.2; Jones C.1; Li G.2
2018-04-01
Source PublicationMolecular Cancer Research
ISSN15573125 15417786
Volume16Issue:4Pages:623-633
Abstract

Lysine to methionine mutations at position 27 (K27M) in the histone H3 (H3.3 and H3.1) are highly prevalent in pediatric high-grade gliomas (HGG) that arise in the midline of the central nervous system. H3K27M perturbs the activity of polycomb repressor complex 2 and correlates with DNA hypomethylation; however, the pathways whereby H3K27M drives the development of pediatric HGG remain poorly understood. To understand the mechanism of pediatricHGGdevelopment driven by H3.3K27M and discover potential therapeutic targets or biomarkers, we established pediatric glioma cell model systems harboring H3.3K27M and performed microarray analysis. H3.3K27M caused the upregulation of multiple cancer/testis (CT) antigens, such as ADAMTS1, ADAM23, SPANXA1, SPANXB1/2, IL13RA2, VCY, and VCX3A, in pediatric glioma cells. Chromatin immunoprecipitation analysis from H3.3K27M cells revealed decreased H3K27me3 levels and increased H3K4me3 levels on the VCX3A promoter. Knockdown of VCX3A by siRNA significantly inhibited the growth of pediatric glioma cells harboring H3.3K27M. Overexpression of VCX3A/B genes stimulated the expression of several HLA genes, including HLA-A, HLA-B, HLA-E, HLA-F, and HLA-G. The expression of VCX3A in pediatric HGG was confirmed using a tissue microarray. Gene set enrichment analysis revealed that CT antigens are enriched in pediatric HGG clinical specimens with H3.3K27M, with the upregulation of IL13RA2 contributing to the enrichment significantly. These results indicate that the upregulation of CT antigens, such as VCX3A and IL13RA2, correlates with pediatric gliomagenesis. Mol Cancer Res; 16(4); 623-33.

DOI10.1158/1541-7786.MCR-17-0460
URLView the original
Indexed BySCI
WOS Research AreaOncology ; Cell Biology
WOS SubjectOncology ; Cell Biology
WOS IDWOS:000429111100006
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.The Institute of Cancer Research, London
2.Universidade de Macau
Recommended Citation
GB/T 7714
Deng H.,Zeng J.,Zhang T.,et al. Histone H3.3K27M mobilizes multiple cancer/testis (CT) antigens in pediatric glioma[J]. Molecular Cancer Research,2018,16(4):623-633.
APA Deng H..,Zeng J..,Zhang T..,Gong L..,Zhang H..,...&Li G..(2018).Histone H3.3K27M mobilizes multiple cancer/testis (CT) antigens in pediatric glioma.Molecular Cancer Research,16(4),623-633.
MLA Deng H.,et al."Histone H3.3K27M mobilizes multiple cancer/testis (CT) antigens in pediatric glioma".Molecular Cancer Research 16.4(2018):623-633.
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