Age-specific signatures of glioblastoma at the genomic, genetic, and epigenetic levels.

TitleAge-specific signatures of glioblastoma at the genomic, genetic, and epigenetic levels.
Publication TypeJournal Article
Year of Publication2013
AuthorsBozdag S, Li A, Riddick G, Kotliarov Y, Baysan M, Iwamoto FM, Cam MC, Kotliarova S, Fine HA
JournalPLoS One
Volume8
Issue4
Paginatione62982
Date Published2013
ISSN1932-6203
KeywordsAdult, Age 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
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.

DOI10.1371/journal.pone.0062982
Alternate JournalPLoS ONE
PubMed ID23658659
PubMed Central IDPMC3639162
Grant List / / Intramural NIH HHS / United States