Histone 3 lysine 9 trimethylation is differentially associated with isocitrate dehydrogenase mutations in oligodendrogliomas and high-grade astrocytomas Journal Article

   

Authors:	Venneti, S.; Felicella, M. M.; Coyne, T.; Phillips, J. J.; Gorovets, D.; Huse, J. T.; Kofler, J.; Lu, C.; Tihan, T.; Sullivan, L. M.; Santi, M.; Judkins, A. R.; Perry, A.; Thompson, C. B.
Article Title:	Histone 3 lysine 9 trimethylation is differentially associated with isocitrate dehydrogenase mutations in oligodendrogliomas and high-grade astrocytomas
Abstract:	Trimethylation of histone 3 lysine 9 (H3K9me3) is a marker of repressed transcription. Cells transfected with mutant isocitrate dehydrogenase (IDH) show increased methylation of histone lysine residues, including H3K9me3, because of inhibition of histone demethylases by 2-hydroxyglutarate. Here, we evaluated H3K9me3 and its association with IDH mutations in 284 gliomas. Trimethylation of H3K9 was significantly associated with IDH mutations in oligodendrogliomas. Moreover, 72% of World Health Organization grade II and 65% of grade III oligodendrogliomas showed combined H3K9me3 positivity and 1p19q codeletion. In astrocytic tumors, H3K9me3 positivity was found in all grades of tumors; it showed a significant relationship with IDH mutational status in grade II astrocytomas but not in grade III astrocytomas or glioblastomas. Finally, H3K9me3-positive grade II oligodendrogliomas, but not other tumor subtypes, showed improved overall survival compared with H3K9me3-negative cases. These results suggest that repressive trimethylation of H3K9 in gliomas may occur in a context-dependent manner and is associated with IDH mutations in oligodendrogliomas but may be differently regulated in high-grade astrocytic tumors. Furthermore, H3K9me3 may define a subset of grade II oligodendrogliomas with better overall survival. Our results suggest variable roles for IDH mutations in the pathogenesis of oligodendrogliomas versus astrocytic tumors.
Keywords:	adolescent; adult; child; middle aged; genetics; methodology; metabolism; cell survival; tumor markers, biological; pathology; tumor marker; dna methylation; histone; histone-lysine n-methyltransferase; nucleotide sequence; oligodendroglioma; dna mutational analysis; astrocytoma; histones; isocitrate dehydrogenase; histone lysine methyltransferase; histocompatibility antigens; histocompatibility antigen; ehmt2 protein, human
Journal Title:	Journal of Neuropathology and Experimental Neurology
Volume:	72
Issue:	4
ISSN:	0022-3069
Publisher:	Oxford University Press
Date Published:	2013-04-01
Start Page:	298
End Page:	306
Language:	English
PUBMED:	23481705
PROVIDER:	scopus
PMCID:	PMC3615673
DOI:	10.1097/NEN.0b013e3182898113
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84877136671&partnerID=40&md5=ff3b4bee9d717918e3a1e7cfd4eca57d
Notes:	--- - "Export Date: 3 June 2013" - "Source: Scopus"

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