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

Sriram Venneti, Michelle Madden Felicella, Thomas Coyne, Joanna J. Phillips, Daniel Gorovets, Jason T. Huse, Julia Kofler, Chao Lu, Tarik Tihan, Lisa M. Sullivan, Mariarita Santi, Alexander R. Judkins, Arie Perry, Craig B. Thompson

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)298-306
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume72
Issue number4
DOIs
StatePublished - 2013

Keywords

  • Astrocytoma
  • Glioma
  • H3K9me3
  • Histone methylation
  • Isocitrate dehydrogenase
  • Oligodendroglioma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Histone 3 lysine 9 trimethylation is differentially associated with isocitrate dehydrogenase mutations in oligodendrogliomas and high-grade astrocytomas'. Together they form a unique fingerprint.

Cite this