Table 1.

Genetic mutations frequently associated with intramedullary astrocytomas.

Gene	Locus	Mutation	Function	Notes	Targeted therapy
H3F3A	1q42	Missense	Histone protein; mutation alters epigenetic regulation of expression of oncogenes	Poor prognosis, classified as WHO Grade 4	Inhibition of demethylases to increase histone methylation, EZH2 inhibitors to prevent heterochromatin formation, CAR T-cell immunotherapy (74).
MGMT	10q26	Methylation of promoter	Removes methyl groups from guanine, countering alkylating agents; mutation renders tumors more susceptible to alkylation	Improved prognosis in high-grade astrocytomas	MGMT inhibitors e.g. O6-benzylguanine, O6-(4-bromothenyl) guanine (75).
BRAF	7q34	Fusion with KIAA1549 or missense	Regulates cell growth, proliferation, differentiation, tumorigenesis; mutation results in constitutive activation	Improved prognosis, frequent occurrence in pilocytic astrocytomas	BRAF-MEK inhibitors, e.g., vemurafenib/cobimetinib (76), dabrafenib/trametinib, encorafenib/binimetinib (77).
IDH1	2q34	Missense	Citric acid cycle enzyme, mutation produces R-2-hydroxyglutarate that alters epigenetic regulation	Improved prognosis, but low frequency in intramedullary astrocytomas	IDH1 inhibitor ivosidenib (78).
TP53	17p13	Missense	Cell cycle regulation, tumor suppressor; mutation promotes tumor formation and growth	Associated with secondary GBM, linked to Li-Fraumeni syndrome	Suppression of mutant p53, restoring wild-type conformation and activity (79).
CKN2A	9p21	Deletion	Tumor suppressor proteins that induce cell cycle arrest; mutation drives proliferation	Poor prognosis
CDK4	12q14	Amplification	Promotes cell cycle progression; mutation drives proliferation	Poor prognosis	CDK4 inhibitor Palbociclib (80).
ATRX	Xq21	Missense, deletion, fusion	Chromatin remodeling and epigenetic regulation; mutation alters genetic expression	Associated with IDH1 mutations, more common in high-grade intramedullary astrocytomas than low-grade	Restoring native chromatin configuration, DNA-damaging agents (81).

CAR, chimeric antigen receptor; WHO, World Health Organization.