Integrating molecular profiling into glioma diagnosis: implications of the WHO-CNS5-2021 classification of adult-type diffuse gliomas in Colombian patients

TL;DR

This study shows how molecular profiling improves glioma diagnosis in Colombian patients according to the 2021 WHO guidelines.

Contribution

The study applies the 2021 WHO CNS5 classification to a Colombian cohort, revealing diagnostic discrepancies and non-canonical mutations.

Findings

23% discordance between histopathologic and molecular classifications was observed.

Molecular profiling identified non-canonical mutations like IDH1 p.R132S affecting prognosis.

Abstract

Gliomas are the most frequent type of primary malignant central nervous system (CNS) tumors, representing a group of heterogeneous neoplasms with variable clinical behavior that require adequate diagnostic accuracy. The identification of molecular biomarkers has recently gained significance for the diagnosis, prognosis, and treatment of CNS tumors; the application of current clinical guidelines is necessary. Our study performed a molecular characterization of gliomas in a cohort of Colombian patients using the recommendations of the 2021 World Health Organization (WHO) CNS 5 classification.

We analyzed 22 Colombian patients with CNS tumors. Molecular techniques including Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA) and methylation-specific MLPA (MS-MLPA) were used to identify mutations in IDH1, IDH2, TERT, and EGFR, as well as 1p/19q co-deletion and MGMT promoter methylation status.

Our results demonstrated a 23% discordance rate between histopathologic and molecular classifications, with most of the discrepancies due to an initial histopathologic classification of glioblastomas, which were molecularly reclassified as astrocytomas. In addition, molecular profiling allowed us to identify non-canonical mutations, including IDH1 p.R132S, which has shown an impact on patient prognosis.

We highlight the importance of incorporating molecular methods to improve diagnostic accuracy and achieve personalized treatments for gliomas, as proposed by the current 2021 WHO CNS 5 tumor classification guidelines. Performing new studies with larger patient cohorts integrating clinical data is necessary to determine the behavior, epidemiology, and therapeutic outcomes of this type of tumor more comprehensively.

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