Article Figures & Data
Figures
- Figure 1.
Hierarchical cluster analysis of patient PA specimens. Gene expression data were filtered, z-score normalized (SD of 1 across all samples for each gene), and subjected to hierarchical cluster analysis as described in the text. The dendrogram on the left displays the relationship of the samples based on their global pattern of gene expression. On the right of the dendrogram is a “heat map” representing gene expression, with each of the 41 samples represented in a row, each probe set represented as a vertical line, and the relative expression of any one gene in any one sample in continuous color scale from low (yellow) to high (dark blue) expression. Age of patient, gender, tumor location, additional features (comment), and NF1 status (Y, NF1-PA; N, non–NF1-PA or sporadic PA) are provided for each of the PA samples studied.
- Figure 2.
Genes differentially expressed in NF1-PAs and sporadic PAs. A, genes differentially expressed in NF1-PAs and sporadic PAs based on SAM at false discovery rate of 0 and a q value of 0. Genes are listed in descending order of significance based on the score assigned by SAM. Genes shown in bold were used for independent validation experiments. B, TAK1-like protein (left), similar to SRGAP2 (middle) and SLC1A3 (right) mRNA expression, was measured by real-time reverse transcription PCR in 10 sporadic PAs and 5 NF1-PAs. Increased TAK1-like protein, similar to SRGAP2 and SLC1A3 mRNA expression, was observed in NF1-PAs when compared with sporadic PAs. C, DCAMKL1 (left), OBFC1 (middle), and MASS1 (right) mRNA expression was measured in an independent set of 10 sporadic PAs and 7 NF1-PAs. Increased DCAMKL1, OBFC1, and MASS1 mRNA expression was observed in NF1-PAs compared with sporadic PAs.
- Figure 3.
Genes differentially expressed in supratentorial and posterior fossa PAs. A, LHX2 (left) and NR2E1 (right) mRNA expression was measured by real-time reverse transcription PCR in an independent series of formalin-fixed, paraffin-embedded supratentorial (ST-PA; n = 10) and posterior fossa (PF-PA; n = 9) PAs. Increased LHX2 and NR2E1 mRNA expression was observed in supratentorial PAs compared with posterior fossa PAs. B, immunohistochemical analysis of PAX3 protein expression in supratentorial and posterior fossa PAs. PAX3 protein expression is shown for a representative posterior fossa PA (left) and a representative supratentorial PA (right). A summary of the PAX3 staining results in posterior fossa and supratentorial PAs from an independent series of samples is shown in the table. The proportion of posterior fossa tumors immunoreactive for PAX3 protein expression was statistically different from that observed in supratentorial tumors (P = 0.020, Fisher's exact test). C, immunohistochemical analysis of LHX2 protein expression in supratentorial and posterior fossa PAs. LHX2 protein expression is shown for a representative posterior fossa PA (left) and a representative supratentorial PA (right). A summary of the LHX2 staining results in posterior fossa and supratentorial PAs from an independent series of samples is shown in the table. The proportion of supratentorial tumors positive for LHX2 protein expression was statistically different from that observed in posterior fossa tumors (P = 0.005, Fisher's exact test). Bar, 50 μm. Arrows, nuclear LHX2 immunoreactivity.
- Figure 4.
Murine brain, astrocyte, and neural stem cell mRNA expression of genes differentially expressed in PAs. A, analysis of the differentially expressed PA genes ( Table 1) in mouse brain and astrocytes. Genes with increased mRNA expression in supratentorial or posterior fossa PAs and neocortical (CTX) or cerebellar (CB) astrocytes are presented. Statistically significant differences (P values by Benjamini-Hochberg–corrected Student's t test) are included for both the original PA microarray data and the astrocyte microarray data. B, LHX2, NR2E1, IRX2, and PAX3 mRNA expression was examined in PN1 and PN30 mouse neocortex and cerebellum (upper), in primary PN1 neocortical and cerebellar astrocytes (middle), as well as in PN1 neocortical and cerebellar neural stem cells (NSC; lower). In each analysis, mRNA levels were normalized to neocortex, neocortical astrocytes, or neocortical neural stem cells (relative value = 1.0). *, P < 0.05.
- Figure 5.
Ependymoma mRNA expression of the genes differentially expressed in PA. A, analysis of the differentially expressed PA genes ( Table 1) in supratentorial and posterior fossa ependymomas. Genes with increased mRNA expression in supratentorial (ST-PA) or posterior fossa (PF-PA) PAs and supratentorial (ST) or posterior fossa (PF) ependymomas are presented. Statistically significant differences (P values by Benjamini-Hochberg–corrected Student's t test) are included for both the original PA microarray data and the ependymoma microarray data. B, immunohistochemical analysis of PAX3 protein expression in supratentorial and posterior fossa ependymomas. PAX3 protein expression is shown for a representative posterior fossa ependymoma (left) and a representative supratentorial ependymoma (right). The immunohistochemistry results for PAX3 protein expression in posterior fossa and supratentorial ependymoma samples are shown in the table. The proportion of posterior fossa tumors with tumoral PAX3 immunoreactivity was statistically different from that observed in supratentorial tumors (P < 0.001, Fisher's exact test). C, immunohistochemical analysis of LHX2 protein expression in supratentorial and posterior fossa ependymomas. LHX2 protein expression is shown for a representative posterior fossa ependymoma (left) and a representative supratentorial ependymoma (right; arrowheads). The immunohistochemistry results for LHX2 protein expression in posterior fossa and supratentorial ependymoma samples are shown in the table. The proportion of supratentorial tumors with LHX2 immunoreactivity was statistically different from that observed in posterior fossa tumors (P < 0.001, Fisher's exact test). Bar, 50 μm.
Tables
- Table 1.
Genes differentially expressed in supratentorial and posterior fossa PA
Unique probe identifier UniGene ID UniGene gene name UniGene gene symbol SAM score Fold change (average ST-PA / average PF-PA) 206140_at Hs.445265 LIM homeobox 2 LHX2 9.23 16.05 211219_s_at Hs.445265 LIM homeobox 2 LHX2 7.80 7.27 241700_at Hs.458973 Zinc finger homeodomain 4 ZFHX4 6.89 3.49 223582_at Hs.482811 Monogenic, audiogenic seizure susceptibility 1 homologue (mouse) MASS1 6.48 5.41 205080_at Hs.436538 Retinoic acid receptor, β RARB 6.15 2.49 236277_at Hs.390616 p21 (CDKN1A)-activated kinase 3 PAK3 6.04 2.61 207443_at Hs.157688 Nuclear receptor subfamily 2, group E, member 1 NR2E1 5.81 9.16 206584_at Hs.69328 Lymphocyte antigen 96 LY96 5.58 3.02 218737_at Hs.144055 Sno, strawberry notch homologue 1 (Drosophila) SBNO1 5.54 1.73 222811_at Hs.72782 Hypothetical protein FLJ11171 FLJ11171 5.50 1.63 1561985_at Hs.335754 Chromosome 14 open reading frame 39 C14orf39 5.34 16.33 1562940_at Hs.568083 cDNA clone IMAGE:5301683 5.33 1.68 228347_at Hs.558398 Sine oculis homeobox homologue 1 (Drosophila) SIX1 5.32 9.53 214830_at Hs.200738 Solute carrier family 38, member 6 SLC38A6 5.30 1.82 226339_at Hs.21187 TruB pseudouridine (ψ) synthase homologue 1 (E. coli) TRUB1 5.28 1.72 204205_at Hs.474853 Apolipoprotein B mRNA editing enzyme, catalytic polypeptide like 3G APOBEC3G 5.12 2.15 201744_s_at Hs.406475 Lumican LUM 5.07 5.08 205905_s_at Hs.549053 MHC class I polypeptide-related sequence A MICA 5.03 1.84 227038_at Hs.48343 Hypothetical protein MGC26963 MGC26963 5.02 2.46 207181_s_at Hs.9216 Caspase 7, apoptosis-related cysteine peptidase CASP7 4.97 1.64 204523_at Hs.181552 Zinc finger protein 140 (clone pHZ-39) ZNF140 4.97 1.64 207250_at Hs.194756 Sine oculis homeobox homologue 6 (Drosophila) SIX6 4.96 9.41 227059_at Hs.444329 Glypican 6 GPC6 4.92 2.51 214078_at Hs.390616 p21 (CDKN1A)-activated kinase 3 PAK3 4.90 2.47 206634_at Hs.503113 Sine oculis homeobox homologue 3 (Drosophila) SIX3 4.89 8.28 226117_at Hs.310640 TRAF-interacting protein with a forkhead-associated domain TIFA 4.81 1.77 202352_s_at Hs.4295 Proteasome (prosome, macropain) 26S subunit, non-ATPase, 12 PSMD12 4.81 1.34 201659_s_at Hs.372616 ADP-ribosylation factor–like 1 ARL1 4.78 1.69 213172_at Hs.79170 Tetratricopeptide repeat domain 9 TTC9 4.74 3.16 214770_at Hs.446291 Macrophage scavenger receptor 1 MSR1 4.74 2.43 231666_at Hs.42146 Paired box gene 3 (Waardenburg syndrome 1) PAX3 −10.96 0.03 228462_at Hs.282089 Iroquois homeobox protein 2 IRX2 −7.47 0.19 210239_at Hs.435730 Iroquois homeobox protein 5 IRX5 −6.18 0.11 1553485_at Hs.350729 Hypothetical protein FLJ32447 FLJ32447 −5.57 0.24 216059_at Hs.42146 Paired box gene 3 (Waardenburg syndrome 1) PAX3 −5.50 0.06 212816_s_at Hs.533013 Cystathionine β-synthase CBS −5.40 0.43 203185_at Hs.379970 Ras association (RalGDS/AF-6) domain family 2 RASSF2 −5.11 0.47 230463_at Hs.445503 Synapsin II SYN2 −4.98 0.33 243879_at Hs.445503 Synapsin II SYN2 −4.75 0.24 212561_at Hs.501857 RAB6 interacting protein 1 RAB6IP1 −4.61 0.66 1553972_a_a Hs.533013 Cystathionine β-synthase CBS −4.52 0.45 -
NOTE: Genes with increased or decreased expression in supratentorial PA are listed in descending order of significance based on the score assigned by SAM.
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Supplementary Data Sharma, et al.
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