title: Age-specific signatures of glioblastoma at the genomic, genetic, and epigenetic levels.
abstract: Age is a powerful predictor of survival in glioblastoma multiforme (GBM) yet the biological basis for the difference in clinical outcome is mostly unknown. Discovering genes and pathways that would explain age-specific survival difference could generate opportunities for novel therapeutics for GBM. Here we have integrated gene expression, exon expression, microRNA expression, copy number alteration, SNP, whole exome sequence, and DNA methylation data sets of a cohort of GBM patients in The Cancer Genome Atlas (TCGA) project to discover age-specific signatures at the transcriptional, genetic, and epigenetic levels and validated our findings on the REMBRANDT data set. We found major age-specific signatures at all levels including age-specific hypermethylation in polycomb group protein target genes and the upregulation of angiogenesis-related genes in older GBMs. These age-specific differences in GBM, which are independent of molecular subtypes, may in part explain the preferential effects of anti-angiogenic agents in older GBM and pave the way to a better understanding of the unique biology and clinical behavior of older versus younger GBMs.
authors: Neuro-Oncology Branch, National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA. serdar.bozdag@marquette.edu
authors: Serdar
authors: S
authors: Bozdag
authors: Aiguo
authors: A
authors: Li
authors: Gregory
authors: G
authors: Riddick
authors: Yuri
authors: Y
authors: Kotliarov
authors: Mehmet
authors: M
authors: Baysan
authors: Fabio M
authors: FM
authors: Iwamoto
authors: Margaret C
authors: MC
authors: Cam
authors: Svetlana
authors: S
authors: Kotliarova
authors: Howard A
authors: HA
authors: Fine
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000235:genetics* / Q000473:pathology; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D006801:Humans; D008297:Male; D035683:MicroRNAs; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D063146:Polycomb-Group Proteins / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D016019:Survival Analysis
chemical_list: D020533:Angiogenesis Inhibitors; D035683:MicroRNAs; D063146:Polycomb-Group Proteins
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