Integrating Molecular Markers Into Glioma Treatment Planning

EP: 1.Redefining Gliomas Through Molecular Classification

EP: 2.Treatment Workflow for IDH-Mutant Gliomas

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EP: 3.Integrating Molecular Markers Into Glioma Treatment Planning

EP: 4.Postsurgical Assessment and Early Management Considerations for IDH-Mutant Gliomas

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Molecular testing workflow begins with immunohistochemistry for IDH1 R132H mutation, which identifies 85% to 90% of IDH-mutant gliomas and provides rapid initial results. This is followed by fluorescence in situ hybridization (FISH) testing for 1p19q codeletion to distinguish between oligodendrogliomas (IDH-mutant with 1p19q codeletion) and astrocytomas (IDH-mutant without codeletion). However, 10% to 15% of patients require next-generation sequencing to identify non-canonical IDH mutations, which can delay diagnosis by several weeks but is crucial for accurate classification.

Additional molecular markers significantly impact treatment planning, particularly CDKN2A/2B homozygous deletion, which automatically upgrades IDH-mutant astrocytomas to grade 4 regardless of histologic appearance. Other alterations like CDK4/6 amplification and growth factor pathway mutations, while not definitively changing diagnosis, warrant closer monitoring and may influence treatment intensity. The ATRX retention status can provide additional diagnostic clues, with retained ATRX more likely indicating IDH wild-type tumors.

Next-generation sequencing becomes mandatory when standard immunohistochemistry returns negative in clinically suspected IDH-mutant cases, as this identifies non-canonical IDH1 mutations and rare IDH2 mutations. Brain stem gliomas represent a particularly important group where molecular testing may reveal IDH alterations that dramatically change prognosis and treatment options. The comprehensive molecular profiling ensures accurate diagnosis and prevents missed opportunities for targeted therapy, particularly as IDH inhibitors become available for these molecularly defined patient populations.