Anatomic mapping of molecular subtypes in diffuse glioma

Area of Science:

• Neuro-oncology
• Molecular Pathology
• Radiology

Background:

• Tumor location is a known prognostic factor in glioma, but its association with specific molecular subtypes and histological variations remains underexplored.
• The cell origin theory suggests molecular features are linked to tumor location, yet detailed anatomic distributions of molecular subtypes require further investigation.
• Existing knowledge on the relationship between molecular phenotype, histological subgroup, and tumor location in gliomas is limited.

Purpose of the Study:

• To investigate the anatomic distribution of distinct molecular subgroups in cerebral diffuse gliomas.
• To explore the consistency between molecular subgroups, histological subtypes, and tumor location.
• To analyze the influence of tumor location, molecular stratification, and histology on patient survival outcomes.

Main Methods:

• Retrospective review of 143 cerebral diffuse glioma cases with available molecular (IDH1/TERT/1p19q) and MRI data.
• Analysis of anatomic distribution across different molecular subgroups and its correlation with histological subtypes.
• Investigation of the impact of tumor location, molecular profile, and histology on clinical outcomes.

Main Results:

• Cerebral diffuse gliomas exhibit varied clinical outcomes based on anatomic location, allowing stratification into five principal molecular subgroups (IDH1/TERT/1p19q status).
• Triple-positive gliomas (IDH1/TERT mutation, 1p19q codeletion) showed significantly better outcomes (median OS 39 months) than TERT mutation-only glioblastomas (median OS 18 months).
• Distinct molecular subgroups displayed characteristic locational distributions consistent with their respective histological subtypes.

Conclusions:

• Each molecular subgroup of glioma possesses a unique anatomic location associated with a distinct clinical outcome.
• Molecular diagnosis serves as a valuable complementary tool for accurate glioma diagnosis.
• Integrating histomolecular diagnosis is crucial for advancing routine clinical practice in neuro-oncology.