F.3 Comprehensive multiplatform analysis of CDKN2A alterations in meningiomas

Background: In meningiomas, CDKN2A/B deletions are associated with poor outcomes but rare in most cohorts (1-5%). Large molecular datasets therefore required to explore these and their relationship other prognostic CDKN2A alterations. Methods: We utilized multidimensional data of 560 meningiomas from 5 independent comprehensively interrogate the spectrum alterations through DNA methylation, copy number variation, transcriptomics, proteomics using an integrated approach. Results: Meningiomas either (partial or homozygous loss) intact gene locus elevated mRNA expression (CDKN2A high ) both had clinical outcomes. Increased was a factor deletion. p16 protein increased tumor grade more aggressive methylation groups. were enriched for similar cell cycling pathways dysregulated at different checkpoints. immunohistochemistry unreliable differentiating between without deletions, positivity expression. hypermethylation, Rb-deficiency, lack response CDK inhibition. Conclusions: These findings support role as biomarker clinically potential therapeutic implications.