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==Primary Author(s)==

==Primary Author(s)==

Linda D Cooley

Linda D Cooley, MD, MBA

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Histopathology – astrocytic morphology – can range from diffuse low-grade glioma to high grade glioma.

Histopathology – astrocytic morphology – can range from diffuse low-grade glioma to high grade glioma.

H3 K27M-mutant gliomas can display a broad spectrum of histological features, including giant, epithelioid, and rhabdoid cells; primitive neuroectodermal tumor–like foci; ependymal-like areas; sarcomatous transformation, as well as features that may wrongly suggest circumscribed gliomas such as neuropil-like islands, pilomyxoid features, ganglionic differentiation, and pleomorphic xanthoastrocytoma-like areas.

H3 K27M-mutant gliomas can display a broad spectrum of histological features, including giant, epithelioid, and rhabdoid cells; primitive neuroectodermal tumor–like foci; ependymal-like areas; sarcomatous transformation, as well as features that may wrongly suggest circumscribed gliomas such as neuropil-like islands, pilomyxoid features, ganglionic differentiation, and pleomorphic xanthoastrocytoma-like areas.

==Immunophenotype==

==Immunophenotype==

|Negative (subset) || ATRX

|Negative (subset) || ATRX

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==Characteristic Chromosomal Aberrations / Patterns==

==Characteristic Chromosomal Aberrations / Patterns==

H3-K27M mutation defines the entity.  K27M mutation occurs in either of 2 genes, H3F3A or HIST1H3B, which encode the histone H3 variants, H3.3 and H3.1, respectively (3).

H3-K27M mutation defines the entity.  K27M mutation occurs in either of 2 genes, H3F3A or HIST1H3B, which encode the histone H3 variants, H3.3 and H3.1, respectively (3).

Cooperating genetic alterations include: TP53 and ATRX mutations. A subset of K27M+ DIPGs have ACVR1 missense mutations (encodes the activin A receptor type-1 transmembrane protein, that lead to activation of the BMP-TGF signaling pathway). Other alterations found in K27M+ DIPGs include PIK3CA mutation, PDGFRA mutation or amplification, PPM1D mutation, and amplification of cell cycle genes including CCND1, CDK4 and CDK6 (3).

Cooperating genetic alterations include: TP53 and ATRX mutations. A subset of K27M+ DIPGs have ACVR1 missense mutations (encodes the activin A receptor type-1 transmembrane protein, that lead to activation of the BMP-TGF signaling pathway). Other alterations found in K27M+ DIPGs include PIK3CA mutation, PDGFRA mutation or amplification, PPM1D mutation, and amplification of cell cycle genes including CCND1, CDK4 and CDK6 (3).

==Genomic Gain/Loss/LOH==

==Genomic Gain/Loss/LOH==

{| class="wikitable sortable"

{| class="wikitable sortable"

|-

|-

! Gene !! Mutation !! Oncogene/Tumor Suppressor/Other !! Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) !! Prevalence (COSMIC/TCGA/Other)

! Mutation % !! Mutation

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|-

| TP53 || R273H || Tumor Suppressor || LOF || 20%

| TP53 || R273H || Tumor Suppressor || LOF || 20%