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Fig. 4 | Acta Neuropathologica Communications

Fig. 4

From: MYC overexpression and SMARCA4 loss cooperate to drive medulloblastoma formation in mice

Fig. 4

MYC/SMARCA4 tumors show similarities to Group 3 MB in gene expression analysis. (A) UMAP clustering of mouse tumors profiled by RNA sequencing and published expression data of pediatric brain tumors (Sturm et al. 2016 [61]). Out of the 14,151 orthologous genes identified between both datasets, the 6,000 most differentially expressed genes within the human dataset were used for clustering. Mouse SHH MB show resemblance to their human counterpart, whereas MYC/SMARCA4 tumors display similarity to both SHH MB and Group 3/4 MB. (B) Hierarchical clustering according to differentially expressed genes shows proximity of MYC/SMARCA4 tumors to the Group 3/4 MB cluster for three samples, whereas tumor 3 clusters with a subset of SHH MB (black arrows). (C) Distance plot shows closest resemblance of both mouse tumor models to SHH MB. Asterisks mark shortest distance. (D) UMAP clustering of mouse tumors and human MB subgroups only (Sturm et al. 2016) according to the 5,000 most differentially expressed genes within the human MB dataset out of 14,151 orthologous genes. MYC/SMARCA4 tumors appear closest to Group 3 MB. (E) Hierarchical clustering confirms proximity of MYC/SMARCA4 tumors to the Group 3/4 MB cluster with exception of tumor 3 (black arrows). (F) Distance plot shows closest resemblance of MYC/SMARCA4 tumors to Group 3 MB. EFT, CIC = Ewing sarcoma family tumor with CIC alteration; HGNET, BCOR = High-grade neuroepithelial tumor with BCOR alteration; NB, FOXR2 = Neuroblastoma with FOXR2 activation; EPN, RELA = Ependymoma with RELA fusion; EPN, YAP = Ependymoma with YAP fusion; ETMR = Embryonal tumor with multilayered rosettes; HGG, G34 = H3F3A G34 mutant high-grade glioma; HGG, IDH = IDH mutant high-grade glioma; HGG, K27 = H3F3A K27 mutant diffuse midline glioma; HGG, MYCN = MYCN-amplified high-grade glioma; HGG, RTK = IDH/H3F3A wild-type high-grade glioma of the receptor tyrosine kinase (RTK) subtype; MB, G3 = MB, Group 3; MB, G4 = MB, Group 4

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