Fig. 2

Copy number alterations (CNA) plot of case #1 (A) and #2 (B) obtained from DNA methylation analysis. Case #1 shows gain of multiple whole chromosomes (2, 7, 9, 11, 12, 15, 19, 20, 21, X, Y), a 4x gain of 1q and segmental gains at chromosome 5 (A). Case #2 shows loss of multiple whole chromosomes (i.e., 3, 6, 10, 11, 12, 13, 14, 15, 17, 18, and 22) (B). SNP-analysis shows LOH of multiple whole chromosomes, including chromosome 13 (C), where RB1 maps, and at region 5q21.3q33.3 (not shown). Unsupervised t-SNE analysis of DNA methylation array profile from the current cases (squares) and 1020 previously published brain tumor reference samples [1, 2, 5]: case #2 clusters into the molecular distinct group of HPAP, whereas case #1 clusters close to it (D) (A IDH - methylation class IDH glioma, subclass astrocytoma; A IDH HG - methylation class IDH glioma, subclass high grade astrocytoma; CONTR INFLAM - methylation class control tissue, inflammatory tumor microenvironment; DLGNT - methylation class diffuse leptomeningeal glioneuronal tumor; EPN PF A - methylation class ependymoma, posterior fossa group A; DMG G34 - methylation class diffuse hemispheric glioma, H3 G34-mutant; GBM MES - methylation class glioblastoma, IDH wildtype, subclass mesenchymal; pedHGG RTK1- methylation class diffuse paediatric-type high grade glioma, RTK1 subtype; pedHGG MYCN - methylation class diffuse paediatric-type high grade glioma, MYCN subtype; GBM RTK I - methylation class glioblastoma, IDH wildtype, subclass RTK I; GBM RTK II - methylation class glioblastoma, IDH wildtype, subclass RTK II; DMG H3.1-K27M - Diffuse midline glioma, H3.1-K27 mutant; DMG H3.3-K27M - Diffuse midline glioma, H3.3-K27 mutant; DMG H3-WT - Diffuse midline glioma, H3 wildtype; DMG H3/MAPK co-altered - includes three classes: Diffuse midline glioma with EZHIP overexpression and FGFR1 mutant, Diffuse midline glioma H3.3-K27 and BRAF mutant, Diffuse midline glioma H3.3-K27 and FGFR1 mutant; HGAP - High-grade astrocytoma with piloid features; HGNET BCOR - methylation class CNS high grade neuroepithelial tumor with BCOR alteration; HPAP - High-grade glioma with pleomorphic and pseudopapillary features; IHG - methylation class infantile hemispheric glioma; LGG DIG/DIA - methylation class low grade glioma, desmoplastic infantile astrocytoma / ganglioglioma; LGG DNT - methylation class low grade glioma, dysembryoplastic neuroepithelial tumor; LGG GG - methylation class low grade glioma, ganglioglioma; LGG MYB - methylation class low grade glioma, MYB/MYBL1; LGG PA MID - methylation class low grade glioma, subclass midline pilocytic astrocytoma; LGG PA PF - methylation class low grade glioma, subclass posterior fossa pilocytic astrocytoma; LGG PA CORT - methylation class pilocytic astrocytoma; LGG RGNT - methylation class low grade glioma, rosette forming glioneuronal tumor; LGG SEGA - methylation class low grade glioma, subependymal giant cell astrocytoma