Evidence for age‐related contributions of DNA damage and epigenetics in brain tumorigenesis
Autor: | Adrian Tira, Lela Buckingham |
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Rok vydání: | 2021 |
Předmět: |
Adult
Male Carcinogenesis DNA damage Guanine medicine.disease_cause Epigenesis Genetic Pathology and Forensic Medicine Young Adult chemistry.chemical_compound medicine Humans Epigenetics Molecular Biology Cyclin-Dependent Kinase Inhibitor p16 Aged Brain Neoplasms Cell growth business.industry Age Factors Brain Original Articles Cell Biology Methylation DNA Methylation Middle Aged chemistry Cancer research Pyrosequencing Female Glioblastoma business Cytosine DNA Damage |
Zdroj: | Int J Exp Pathol |
ISSN: | 1365-2613 0959-9673 |
Popis: | Glioblastoma (GBM) is a highly malignant primary brain tumour displaying rapid cell proliferation and infiltration. GBM primarily occurs at older age; however, younger populations have also been affected. In GBM and other cancers, genetic and epigenetic alterations promote tumorigenesis causing increased cell proliferation and invasiveness. This investigation explored epigenetic events as contributing factors, especially in gliomas that arise in patients aged 40-60 years. Furthermore, DNA damage in tumours with respect to age was assessed. Archival fixed tissues from 88 cases of glioblastoma and adjacent non-malignant tissues were tested. Global methylation and DNA damage were measured using ELISA detection of 5-methyl cytosine and 8-hydroxy guanine, respectively. IDH mutations and CDKN2 promoter hypermethylation were analysed by pyrosequencing. Tumour tissue was hypomethylated compared with non-malignant tissue (P = .001), and there was a trend towards increased methylation with increasing age. There was a significant increase in DNA damage in patients older than forty years compared with those aged forty years or younger (P = .035). CDKN2 promoter methylation levels followed the age trends of global methylation in this patient group. Patients younger than 60 had more frequently mutated IDH (P = .004). Conclusions: The data support the potential of epigenetic factors in promoting tumorigenesis in younger patients, while increased DNA damage contributes to tumorigenesis in the older patients. |
Databáze: | OpenAIRE |
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