Fig. 1: Tumors of the DNA methylation class HGG-MYCN carry MYCN amplifications and TP53 mutations.

a UMAP of global DNA methylation profiling of 2514 cases of multiple brain tumor entities including the most common brain tumors as well as potential differential diagnoses including 47 HGG-MYCN using the 10,000 most differentially methylated CpG sites. b Age distribution of n = 89 HGG-MYCN tumors with a median age of 8 years (bounds of box = 3–13, whiskers = min:1, max:22). c Sex distribution of 106 HGG-MYCN. d 47 HGG-MYCN were screened for TP53 mutations, of which 68% carried a mutation. e The same 47 cases as in (d) were analyzed for their MYCN status. f Of the same 47 cases shown in (d) and (e), only 8% carried no TP53 or MYCN alteration, whereas 36% of those carry both alterations. g Tumors can be found throughout the entire brain with the majority of cases located in the temporal and frontal lobes. h Heatmap showing copy number variations of 47 HGG-MYCN. The copy number profile of such tumors is imbalanced with a clearly visible MYCN amplification (Chr. 2), highlighted by the arrow. MYCN amplifications can also be detected by FISH analysis (representative case shown in (i), three independent tumors showing this amplification were analyzed), while IHC may serve as a surrogate marker (representative case in (j), the same three tumors were analyzed). k Nuclear p53 accumulation indicating impaired p53 function can be detected by IHC (representative case, three independent tumors were analyzed). l Representative CNV plot of a HGG-MYCN with a magnification of chromosome 2 with the MYCN amplification (CNV plots of 47 tumors were generated). Scale bar in i = 5 μm, in j & k = 50 μm. Source data are provided as a Source Data file.