Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The oligodendrocyte lineage genes OLIG1 and OLIG2 have been reported as potential diagnostic markers for oligodendrogliomas [Lu et al. (2001) Proc Natl Acad Sci USA 98:10851-10856; Marie et al. (2001) Lancet 358:298-300]. We investigated the mRNA expression of OLIG1 and OLIG2, as well as four other genes involved in oligodendrocyte development ( E2A, HEB, NKX2.2, and PDGFRA) in a panel of 70 gliomas, including 9 oligodendrogliomas, 11 anaplastic oligodendrogliomas, 5 oligoastrocytomas, 10 anaplastic oligoastrocytomas, 10 diffuse astrocytomas, 10 anaplastic astrocytomas, and 15 glioblastomas. Most tumors demonstrated higher transcript levels of these genes as compared to non-neoplastic adult brain tissue. Four glioblastomas showed markedly increased PDGFRA mRNA expression due to PDGFRA gene amplification. Statistical analyses revealed no significant expression differences between oligodendroglial and astrocytic tumors. In oligodendroglial tumors, expression of the six genes was not significantly correlated to loss of heterozygosity on chromosome arms 1p and 19q. Thus, expression of the investigated oligodendrocyte lineage genes is up-regulated relative to non-neoplastic brain tissue in the majority of oligodendroglial and astrocytic tumors, suggesting that glioma cells are arrested in or recapitulate molecular phenotypes corresponding to early stages of glial development. However, the determination of mRNA expression of these genes by means of reverse transcription-PCR does not appear to be diagnostically useful as a marker for oligodendrogliomas.
 ...
PMID:Expression of oligodendrocyte lineage genes in oligodendroglial and astrocytic gliomas. 1473 Apr 54

Two recurrent mutations, K27M and G34R/V, in H3F3A, encoding non-canonical histone H3.3, are reported in pediatric and young adult gliomas, whereas G34W mutation is prevalent in bone tumors. In contrast to K27M mutation, it remains elusive how G34 mutations affect the epigenome. Here we performed whole-genome bisulfite sequencing of four G34R-mutated gliomas and the G34V-mutated glioma cell line KNS-42 for comparison with gliomas harboring K27M and no mutations in H3F3A and with G34W-mutated bone tumors. G34R-mutated gliomas exhibited lower global methylation levels, similar CpG island (CGI) methylation levels, and compromised hypermethylation of telomere-proximal CGIs, compared to the other two glioma subgroups. Hypermethylated regions specific to G34R-mutated gliomas were enriched for CGIs, including those of OLIG1, OLIG2, and canonical histone genes in the HIST1 cluster. They were notably hypermethylated in osteosarcomas with, but not without, G34W mutation. Independent component analysis revealed that G34 mutation-specific components shared a significant similarity between glioma and osteosarcoma, suggesting that G34 mutations exert characteristic methylomic effects regardless of the tumor tissue-of-origin. CRISPR/Cas9-mediated disruption of G34V-allele in KNS-42 cells led to demethylation of a subset of CGIs hypermethylated in G34R-mutated gliomas. These findings will provide a basis for elucidating epigenomic roles of G34 oncohistone in tumorigenesis.
 ...
PMID:Base-resolution methylomes of gliomas bearing histone H3.3 mutations reveal a G34 mutant-specific signature shared with bone tumors. 3299 76