Molecular neuro-oncology in clinical practice: a new horizon

Area of Science:

• Neuro-oncology
• Molecular Pathology
• Genomics

Background:

• Primary brain tumors exhibit significant heterogeneity in histology, genetics, and patient outcomes.
• The World Health Organization (WHO) classification of CNS tumors provides standardized diagnostic criteria but lacks integration of molecular advancements.
• Recent clinical trials highlight the importance of molecular markers like MGMT promoter methylation and 1p/19q codeletions.

Purpose of the Study:

• To review the impact of molecular classification on understanding primary brain tumors.
• To discuss the identification of novel molecular subgroups within gliomas and medulloblastomas.
• To highlight the current limitations of molecular approaches in predicting therapeutic efficacy.

Main Methods:

• Review of recent clinical trials and large-scale molecular profiling studies.
• Analysis of genetic mutations (IDH1, IDH2, H3F3, ATRX, CIC) in glioma subclassification.
• Examination of transcriptome-based classification in medulloblastoma variants.

Main Results:

• Molecular profiling has identified distinct glioma subgroups based on mutations in IDH1, IDH2, H3F3, ATRX, and CIC, correlating with age, location, and prognosis.
• Routine assessment of MGMT promoter methylation and 1p/19q codeletions are now standard in specific brain tumor types.
• Transcriptome analysis has defined four medulloblastoma variants with potential as targets for novel therapies.

Conclusions:

• Molecular classification significantly refines brain tumor diagnosis and subtyping beyond traditional histology.
• While molecular markers aid in characterizing brain tumors, they currently do not predict patient response to therapy.
• Further research into molecularly defined subgroups is crucial for developing targeted therapeutic strategies for primary brain tumors.