Whole-Exome Sequencing Reveals Recurrent but Heterogeneous Mutational Profiles in Sporadic WHO Grade 1 Meningiomas.

Human WHO grade 1 meningiomas are generally considered benign tumors; despite this, they account for ≈50% of all recurrent meningiomas. Currently, limited data exist about the mutational profiles of grade 1 meningiomas and patient outcome. We investigated the genetic variants present in 32 WHO grade 1 meningiomas using whole exome sequencing, and correlated gene mutational profiles with tumor cytogenetics and patient outcome. Overall, WHO grade 1 meningiomas harbored numerous and heterogeneous genetic variants, which most frequently affected the (47%) gene and to a less extent the (22%), (16%), (13%), (13%), (9%), (6%), (6%), (3%), and (3%) genes. Notably, non-synonymous genetic variants of and were restricted to diploid meningiomas, whereas mutations were only found among tumors that showed -22/22q (with or without a complex karyotype). Based on mutations and tumor cytogenetics, four genetic profiles were defined with an impact on patient recurrence-free survival (RFS). These included (1) two good-prognosis tumor subgroups-diploid meningiomas (n=9) and isolated -22/22q associated with mutation (n=7)-with RFS rates at 10 y of 100%; and (2) two subgroups of poor-prognosis meningiomas-isolated -22/22q without mutation (n=3) and tumors with complex karyotypes (n=11)-with a RFS rate at 10 y of 48% (p=0.003). Our results point out the existence of recurrent but heterogeneous mutational profiles in WHO grade 1 meningiomas which have an impact on patient outcome.