Genetic and epigenetic characterization of low-grade gliomas reveals frequent methylation of the MLH3 gene
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26303387
DOI
10.1002/gcc.22266
Knihovny.cz E-zdroje
- MeSH
- astrocytom genetika metabolismus MeSH
- epigeneze genetická * MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- metylace DNA * MeSH
- MutL proteiny MeSH
- nádorové biomarkery MeSH
- nádory mozku genetika metabolismus MeSH
- oligodendrogliom genetika metabolismus MeSH
- prognóza MeSH
- stupeň nádoru MeSH
- transportní proteiny genetika metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- MLH3 protein, human MeSH Prohlížeč
- MutL proteiny MeSH
- nádorové biomarkery MeSH
- transportní proteiny MeSH
Diffuse astrocytomas and oligodendrogliomas (WHO grade II) are the most common histological subtypes of low-grade gliomas (LGGs). Several molecular and epigenetic markers have been identified that predict tumor progression. Our aim was in detail to investigate the genetic and epigenetic background of LGGs and to identify new markers that might play a role in tumor behavior. Twenty-three patients with oligodendroglioma or oligoastrocytoma (LGO) and 22 patients with diffuse astrocytoma (LGA) were investigated using several molecular-cytogenetic and molecular methods to assess their copy number variations, mutational status and level of promoter methylation. The most frequent findings were a 1p/19q codeletion in 83% of LGO and copy-neutral loss of heterozygosity (CN-LOH) of 17p in 72% of LGA. Somatic mutations in the isocitrate dehydrogenase 1 or 2 (IDH1/IDH2) genes were detected in 96% of LGO and 91% of LGA. The O-6-methylguanine-DNA-methyltransferase (MGMT) promoter was methylated in 83% of LGO and 59% of LGA. MutL homolog 3 (MLH3) promoter methylation was observed in 61% of LGO and 27% of LGA. Methylation of the MGMT promoter, 1p/19q codeletion, mutated IDH1, and CN-LOH of 17p were the most frequent genetic aberrations in LGGs. The findings were more diverse in LGA than in LGO. To the best of our knowledge, this is the first time description of methylation of the MLH3 gene promoter in LGGs. Further studies are required to determine the role of the methylated MLH3 promoter and the other aberrations detected.
Cytogenetic Department Institute of Hematology and Blood transfusion Prague 2 Czech Republic
Institute of Physiology 1st Faculty of Medicine Charles University Prague 2 Czech Republic
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