Associated with LGG and HGG, respectively (Table 6). In LGG, the top

Associated with LGG and HGG, respectively (Table 6). In LGG, the top two GO terms were “DNA binding”, and “regulation of transcription, DNA-dependent”. In HGG, the top two GO terms were “neuronal cell body”, and “defense response to bacterium”. ToGenes Found to Associate with GliomasTo identify specific genes associated with gliomas, we pooled all genomic aberrations occurred in at least six tumor samples. After filtered our data based on known variations found in the controls and Database of Genomic 1676428 Variants (hg18.v8) (http://projects. tcag.ca/variation/), we had 24 genes and the related information was summarized (chromosome location, aberration category, tumor grading) (Table 4). These genes are all clustered on 1p, 7q, and 19q. Among them, 17 genes are only gains, and three of other genes, VN1R2, VN1R4 and ZNF677, have all three types 22948146 of genomic aberrations ain, loss and cnLOH. Referencing to the annotation of the OMIM Morbid Map (http://www.ncbi.nlm.nih. gov/omim), we found that AASS, TAS2R16 and TSPAN12 are previously identified to be disease-related and associated with “hyperlysinemia”, “alcohol dependence” and “exudative vitreoretinopathy”, respectively.Genomic Aberration Patterns in GliomasTable 5. Pathway analysis of genes involved in genomic aberration in LGG (A) and HGG (B).(A) LGG Pathway name Arachidonic acid metabolism Linoleic acid metabolism alpha-Linolenic acid metabolism Ether lipid metabolism Glycerophospholipid metabolism Prion diseases GnRH signaling pathway Long-term depression Vascular smooth muscle contraction VEGF signaling pathway Fc epsilon RI signaling pathway Fatty acid metabolism (B) HGG Pathway name Metabolic pathways Neuroactive ligand-receptor interaction Calcium signaling pathway Melanogenesis HDAC-IN-3 Fructose and mannose metabolism Lysine degradation Androgen and estrogen metabolism Glycerolipid metabolism Glycosaminoglycan degradation Vibrio cholerae infection Note: R indicates the ratio of enrichment. doi:10.1371/journal.pone.0057168.t005 Observed number 14 5 4 3 2 2 2 2 2 2 Expected number 6.21 1.48 1.02 0.58 0.2 0.25 0.26 0.25 0.12 0.31 R 2.25 3.37 3.92 5.14 10.08 7.97 7.62 7.97 16.32 6.47 FDR 6.(��)-Hexaconazole web 00E202 6.00E202 6.00E202 6.00E202 6.00E202 6.00E202 6.00E202 6.00E202 6.00E202 7.28E202 Observed number 9 7 6 7 8 6 9 7 9 7 7 4 Expected number 1.35 0.67 0.43 0.82 1.61 0.84 2.38 1.63 2.71 1.78 1.85 1.01 R 6.69 10.41 13.87 8.57 4.97 7.14 3.78 4.28 3.32 3.94 3.78 3.96 FDR 1.00E204 1.00E204 1.00E204 2.00E204 2.10E203 2.10E203 5.50E203 9.60E203 1.14E202 1.28E202 1.45E202 9.55Eour current knowledge, tumors often alter cellular processes, such as proliferation, growth, programmed death, differentiation, division, mutation-induced DNA damage, and repair [1]. All these newly discovered distinct function categories may introduce features of primary (low-grade) or malignant (high-grade) tumors.Correlating Copy Number Variation with Gene ExpressionWe used real-time qPCR to validate the expression of seven identified genes: AASS, CYP2J2, CYP4A11, PLA2G2A, PLA2G5, PTEN, and RB1. First, all genes showed increased expression when compared in the two tumor grades (HGG vs. LGG) (Table 2). CYP2J2, CYP4A11, PLA2G5 and PTEN exhibited even over 10 fold changes. We did not compare the gene expressions between the tumors and the controls, their corresponding blood cells, due to the tissue-specific nature of the gene expression. Of the seven genes, we noticed RB1 gains in HGG and losses in both grades. Other different aber.Associated with LGG and HGG, respectively (Table 6). In LGG, the top two GO terms were “DNA binding”, and “regulation of transcription, DNA-dependent”. In HGG, the top two GO terms were “neuronal cell body”, and “defense response to bacterium”. ToGenes Found to Associate with GliomasTo identify specific genes associated with gliomas, we pooled all genomic aberrations occurred in at least six tumor samples. After filtered our data based on known variations found in the controls and Database of Genomic 1676428 Variants (hg18.v8) (http://projects. tcag.ca/variation/), we had 24 genes and the related information was summarized (chromosome location, aberration category, tumor grading) (Table 4). These genes are all clustered on 1p, 7q, and 19q. Among them, 17 genes are only gains, and three of other genes, VN1R2, VN1R4 and ZNF677, have all three types 22948146 of genomic aberrations ain, loss and cnLOH. Referencing to the annotation of the OMIM Morbid Map (http://www.ncbi.nlm.nih. gov/omim), we found that AASS, TAS2R16 and TSPAN12 are previously identified to be disease-related and associated with “hyperlysinemia”, “alcohol dependence” and “exudative vitreoretinopathy”, respectively.Genomic Aberration Patterns in GliomasTable 5. Pathway analysis of genes involved in genomic aberration in LGG (A) and HGG (B).(A) LGG Pathway name Arachidonic acid metabolism Linoleic acid metabolism alpha-Linolenic acid metabolism Ether lipid metabolism Glycerophospholipid metabolism Prion diseases GnRH signaling pathway Long-term depression Vascular smooth muscle contraction VEGF signaling pathway Fc epsilon RI signaling pathway Fatty acid metabolism (B) HGG Pathway name Metabolic pathways Neuroactive ligand-receptor interaction Calcium signaling pathway Melanogenesis Fructose and mannose metabolism Lysine degradation Androgen and estrogen metabolism Glycerolipid metabolism Glycosaminoglycan degradation Vibrio cholerae infection Note: R indicates the ratio of enrichment. doi:10.1371/journal.pone.0057168.t005 Observed number 14 5 4 3 2 2 2 2 2 2 Expected number 6.21 1.48 1.02 0.58 0.2 0.25 0.26 0.25 0.12 0.31 R 2.25 3.37 3.92 5.14 10.08 7.97 7.62 7.97 16.32 6.47 FDR 6.00E202 6.00E202 6.00E202 6.00E202 6.00E202 6.00E202 6.00E202 6.00E202 6.00E202 7.28E202 Observed number 9 7 6 7 8 6 9 7 9 7 7 4 Expected number 1.35 0.67 0.43 0.82 1.61 0.84 2.38 1.63 2.71 1.78 1.85 1.01 R 6.69 10.41 13.87 8.57 4.97 7.14 3.78 4.28 3.32 3.94 3.78 3.96 FDR 1.00E204 1.00E204 1.00E204 2.00E204 2.10E203 2.10E203 5.50E203 9.60E203 1.14E202 1.28E202 1.45E202 9.55Eour current knowledge, tumors often alter cellular processes, such as proliferation, growth, programmed death, differentiation, division, mutation-induced DNA damage, and repair [1]. All these newly discovered distinct function categories may introduce features of primary (low-grade) or malignant (high-grade) tumors.Correlating Copy Number Variation with Gene ExpressionWe used real-time qPCR to validate the expression of seven identified genes: AASS, CYP2J2, CYP4A11, PLA2G2A, PLA2G5, PTEN, and RB1. First, all genes showed increased expression when compared in the two tumor grades (HGG vs. LGG) (Table 2). CYP2J2, CYP4A11, PLA2G5 and PTEN exhibited even over 10 fold changes. We did not compare the gene expressions between the tumors and the controls, their corresponding blood cells, due to the tissue-specific nature of the gene expression. Of the seven genes, we noticed RB1 gains in HGG and losses in both grades. Other different aber.