Genome-Wide Association Studies of Copy Number Variation in Glioblastoma

Copy-number variation (CNV) constitutes a large proportion of total genomic variation and is increasingly recognized to be an extremely important risk factor for cancer. To examine the role of CNVs in glioblastoma, a genome-wide association study of CNVs in glioblastoma was conducted by assaying 221 tumor tissues and 28 normal tissues samples from primary glioblastoma multiform patients in TCGA project. CNVs were measured by the Affymetrix Genome-Wide Human SNP Array 6.0 with 906,600 SNPs and more than 946,000 probes for the detection of copy number variation. CNVs were called by the modified Hidden Markov Models (HMM) and 163024 CNV loci were detected. A total of 197 CNV loci with P-value<;3.06*10-7 showed significant association with glioblastoma. We also did group association tests of CNV with glioblastoma by gene and pathway. We identified 169 genes with P-values <;4.77*10-6, including oncogene, tumor suppressor genes, transcription factor and transcription activator genes, which were significantly associated with glioblastoma. We also identified 15 significantly associated pathways with glioblastoma with FDR P-values<;0.05. These significant pathways include Metabolism of xenobiotics by cytochrome P450, Calcium signaling pathway, Axon guidance, Colorectal cancer, Tight junction,Regulation of eIF2 pathway and Glioma. Our results provide important clues for investigation of the mechanisms and drug targets of glioblastoma.