Table 2:

Molecular Markers of Glioma

Molecular Markers	Identification	Primary Outcome Difference	Comments
IDH1/IDH2 Mutation	Histological Stain DNA sequencing IDH1 (Codon 132) IDH2 (Codon 172)	Tumors harboring IDH mutations carry a much higher overall survival rate and may offer additional targeting or therapeutic strategies	The most common IDH mutation in glioma is IDH1 R132H
1p/19q Co-Deletion	FISH NGS (with copy number information)	1p/19q co-deletion is a defining feature of ogligodendroglial tumors and a predictor of favorable response among other gliomas	Almost always co-occurs with IDH mutations so disagreement between the two should raise concerns for false positives in deletion detection
ATRX Mutation	Histological Stain (loss of nuclear ATRX expression indicates presence of ATRX mutation) DNA Sequencing	Typically used as a broad classifier for well differentiated astrocytic glioma No prognostic indication	ATRX mutation closely correlates with IDH and TP53 mutations but is mutually exclusive with 1p/19q co-deletion
TP53 Mutation	Histological Staining (nuclear localization) DNA sequencing	Supportive in diagnosis for IDH mutant astrocytoma No prognostic indication	Nuclear localization of TP53 can reflect mutation of the gene but sequencing should still confirm
H3K27m Mutation	Histological Staining for specific mutation protein DNA Sequencing	Prognostically can indicate poor survival in pediatric glioblastomas	Typically present in diffuse gliomas in midline locations such as DIPG
H3G34 Mutation	Histological Staining for specific mutation proteins NGS	Associated with poor prognosis in mainly diffuse hemispheric gliomas in children and young adults	The mutations associated with H3G4 are missense and result in G34R or G34V alterations
BRAF Alteration	Histological Stain for mutation specific proteins (V600E Mutation) DNA Sequencing FISH (KIAA1549-BRAF fusion)	BRAF V600E mutation typically correlates with increased risk of recurrence in pediatric gliomas	BRAF V600E mutational IHC histological stains can be difficult to interpret
RELA Fusion	FISH	RELA fusion clinically defines 70% of childhood supratentorial ependymomas No prognostic indication	Fusion is between RELA and C19orf95 L1CAM expression on histology can correlate with presence of RELA fusion
YAP1 Fusion	FISH NGS	Diagnostically characteristic of a subset of childhood supratentorial ependymomas No prognostic indication	Fusion typically occurs with MAMLD1 but is not exclusive