Background NRCAM, a neuronal cell adhesion molecule, has been implicated in glioma biology through splicing alterations reported by prior studies. However, the relative contributions of genomic and epigenetic mechanisms to NRCAM dysregulation in gliomas remain unclear.

Methods We analyzed glioma datasets from The Cancer Genome Atlas (TCGA) using UCSC Xena and cBioPortal. Copy number variation (CNV), DNA methylation (Illumina 450K arrays), and mutation profiles were assessed for NRCAM. Kaplan Meier survival analyses were performed with Xena, stratifying patients by copy number status and methylation state. Correlations between mutation burden and fraction genome altered were evaluated using Spearman and Pearson methods.

Results Somatic mutations in NRCAM were rare across TCGA gliomas. In contrast, CNV and methylation changes were frequent and clinically relevant. Copy number gains at the NRCAM locus were associated with significantly shorter overall survival, while higher methylation of NRCAM correlated with improved survival outcomes. NRCAM mutation count did not show a linear correlation with fraction genome altered (FGA), suggesting these alterations are largely independent of overall genomic instability. The findings highlight copy number imbalance and epigenetic regulation as predominant mechanisms of NRCAM dysregulation.

Conclusion NRCAM is recurrently dysregulated in gliomas through copy number alterations and DNA methylation, both of which stratify patient survival. Together with previously reported splicing deregulation, these data suggest that NRCAM functions as a multilayered regulator of glioma progression. NRCAM methylation may represent a prognostic biomarker, while therapeutic modulation of NRCAM warrants further investigation.

The authors have declared no competing interest.

This study did not receive any funding

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