EPCO-47. HETEROZYGOUS CDKN2A LOSS IS ASSOCIATED WITH HIGHER RECURRENCE AND LOWER SURVIVAL IN HIGH-, BUT NOT LOW-GRADE MENINGIOMAS

Abstract

Abstract INTRODUCTION Homozygous loss of CDKN2A/B is known to be associated with more aggressive meningiomas and is now considered in the updated criteria for WHO grading. The relevance of heterozygous loss (hetloss) of CDKN2A/B is less clear and the potential association of hetloss CDKN2A with aggressive meningioma phenotype remains underexplored. OBJECTIVE We sought to understand the clinical associations of hetloss CDKN2A meningiomas. METHODS Clinical and whole exome sequencing (WES) data for patients who underwent resection of sporadic meningiomas were reviewed and analyzed. RESULTS Of the 564 meningiomas included, 16 tumors harbored a heterozygous mutation of CDKN2A; 6 of these were low-grade (WHO grade I) and 10 were high-grade (grade II or III). CDKN2A hetloss meningiomas were more likely to be high-grade (p=0.03) and to be diagnosed at older ages (p=0.04) than wild type (WT). Compared to high-grade hetloss meningiomas, low-grade ones were more likely to have elevated proliferative index (p=0.04) and were more common along the skull base (p=0.04). Low-grade meningiomas with hetloss CDKN2A compared to WT ones were more likely to be symptomatic (p=0.023); there was no difference in the tumor make-up or progression free survival (PFS) (p=0.4). High-grade hetloss CDKN2A meningiomas, however, had higher mitotic count (p=0.014), increased chromosomal instability (p=0.004), and higher recurrence rates (p< 0.001), as well as shorter PFS (p< 0.001) and decreased overall survival (OS) (p=0.002), compared to high-grade WT meningiomas. These findings remained significant amongst high-grade hetloss CDKN2A meningiomas even when controlling for underlying NF2 mutation. CONCLUSION Heterozygous loss of CDKN2A is associated with more aggressive histological and genomic characteristics in high-grade meningiomas. Additionally, high-grade meningiomas with hetloss CDKN2A differ from those without the mutation with higher recurrence rates and shorter PFS and lower OS, irrespective of underlying somatic NF2 mutation. These findings may have clinical implications for management.