Molecular alterations of pediatric gliomas. A: Pilocytic astrocytoma is the most frequent PLGA subtype. B and C: Most of these tumors are characterized by a duplication involving the BRAF kinase domain (array comparative genomic hybridization) (B), which leads most frequently to a novel KIAA1549-BRAF fusion (C).The black bar in B represents an approximately 2 megabase duplicated segment. D: Additional alterations that may be found in PLGAs include a BRAF p.V600E mutation, which may be detected by mutation-specific antibodies (negative non-neoplastic elements, arrows). E: A particular devastating subset of pediatric high-grade gliomas is DIPG, which diffusely expands the pons and may be diagnosed on clinical grounds (arrow). F: Histologically it overlaps with other diffuse gliomas (grades II to IV), but it is uniformly fatal. G and H: Epigenetic alterations typical of this tumor include global hypomethylation which may be tested with antibodies against 5mC (G) and loss of H3K27me3 (preserved labeling in vessels, arrows) (H). I: Most DIPGs have a H3F3A (H3K27M) mutation which is also associated with poor prognosis and may be detected by mutation-specific antibodies. Original magnification: ×400 (A and G–I); ×600 (D and F); DIPG, diffuse intrinsic pontine glioma; H3K27M, methionine 27 mutation in histone 3 variant; H3K27me3, histone 3 K27 trimethylation; PLGA, pediatric low-grade astrocytoma; 5mC, 5-methylcytosine.