Genetic Polymorphisms in Meningioma Formation and Progression

Sporadic meningiomas are common tumors of the arachnoid membrane that arise within the general population. Approximately half of these tumors arise through inactivation of the NF2 tumor suppressor as determined by loss of heterozygosity (LOH) of 22q, the chromosome arm where the NF2 locus is located. Recently, SNP309, a single nucleotide polymorphism in the promoter region of MDM2, was found to accelerate tumor progression by increasing levels of MDM2 protein, a negative regulator of p53. This study investigated a cohort of 92 sporadic meningioma patients and found that in those with both SNP309 and LOH of the NF2 locus, 45.5% had high grade tumors compared to only 13.6% of those who retained both 22q alleles (p = 0.019). In those with LOH of 22q but not SNP309, males had significantly higher tumor grade (p = 0.022). However, among those with LOH of 22q and SNP309, gender and tumor progression were independent, (p = 1.00). This suggests SNP309’s masking of the gender differentation in meningioma progression. This study established the prominence of the p53 pathway in meningioma progression and proposes a molecular model supported by the results.