Age-specific signatures of glioblastoma at the genomic, genetic, and epigenetic levels. PLoS One 2013;8(4):e62982
Date
05/10/2013Pubmed ID
23658659Pubmed Central ID
PMC3639162DOI
10.1371/journal.pone.0062982Scopus ID
2-s2.0-84876895426 (requires institutional sign-in at Scopus site) 53 CitationsAbstract
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.
Author List
Bozdag S, Li A, Riddick G, Kotliarov Y, Baysan M, Iwamoto FM, Cam MC, Kotliarova S, Fine HAMESH terms used to index this publication - Major topics in bold
AdultAge Factors
Aged
Aging
Angiogenesis Inhibitors
Brain Neoplasms
DNA Copy Number Variations
DNA Methylation
Epigenesis, Genetic
Exons
Female
Gene Expression Regulation, Neoplastic
Glioblastoma
Humans
Male
MicroRNAs
Middle Aged
Neovascularization, Pathologic
Polycomb-Group Proteins
Polymorphism, Single Nucleotide
Survival Analysis
