Open AccessAge-Specific Signatures of Glioblastoma at the Genomic, Genetic, and Epigenetic Levels
Author(s) -
Serdar Bozdag,
Aiguo Li,
Gregory Riddick,
Yuri Kotliarov,
Mehmet Baysan,
Fabio Iwamoto,
Margaret C. Cam,
Svetlana Kotliarova,
Howard A. Fine
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0062982
Subject(s) - dna methylation , epigenetics , biology , gene , genetics , microrna , glioblastoma , exome , snp , methylation , computational biology , genomics , exome sequencing , bioinformatics , gene expression , cancer research , genome , single nucleotide polymorphism , genotype , phenotype
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.