title: Genetic and epigenetic characterization of low-grade gliomas reveals frequent methylation of the MLH3 gene.
abstract: 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.
authors: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and 1st Faculty of Medicine, Charles University, Prague 2, Czech Republic.
authors: Halka
authors: H
authors: Lhotska
authors: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and 1st Faculty of Medicine, Charles University, Prague 2, Czech Republic.
authors: Zuzana
authors: Z
authors: Zemanova
authors: Department of Molecular Genetics, Institute of Hematology and Blood Transfusion, Prague 2, Czech Republic.
authors: Hana
authors: H
authors: Cechova
authors: Cytogenetic Department, Institute of Hematology and Blood transfusion, Prague 2, Czech Republic.
authors: Sarka
authors: S
authors: Ransdorfova
authors: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and 1st Faculty of Medicine, Charles University, Prague 2, Czech Republic.
authors: Libuse
authors: L
authors: Lizcova
authors: Department of Neurosurgery, Central Military Hospital and 1st Faculty of Medicine, Charles University, Prague 6, Czech Republic.
authors: Filip
authors: F
authors: Kramar
authors: Department of Molecular Genetics, Institute of Hematology and Blood Transfusion, Prague 2, Czech Republic.
authors: Zdenek
authors: Z
authors: Krejcik
authors: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and 1st Faculty of Medicine, Charles University, Prague 2, Czech Republic.
authors: Karla
authors: K
authors: Svobodova
authors: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and 1st Faculty of Medicine, Charles University, Prague 2, Czech Republic.
authors: Dagmar
authors: D
authors: Bystricka
authors: Department of Neurosurgery, Central Military Hospital and 1st Faculty of Medicine, Charles University, Prague 6, Czech Republic.
authors: Petr
authors: P
authors: Hrabal
authors: Institute of Physiology, 1st Faculty of Medicine, Charles University, Prague 2, Czech Republic.
authors: Alena
authors: A
authors: Dohnalova
authors: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and 1st Faculty of Medicine, Charles University, Prague 2, Czech Republic.|Cytogenetic Department, Institute of Hematology and Blood transfusion, Prague 2, Czech Republic.
authors: Kyra
authors: K
authors: Michalova
mesh_terms: D001254:Astrocytoma / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070956:MutL Proteins; D060787:Neoplasm Grading; D009837:Oligodendroglioma / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C403623:MLH3 protein, human; D000070956:MutL Proteins