Molecular Profiling of 22 Primary Atypical Meningiomas Shows the Prognostic Significance of 18q Heterozygous Loss and CDKN2A/B Homozygous Deletion on Recurrence-Free Survival

SIMPLE SUMMARY: The post-surgical treatment of atypical meningiomas is controversial in cases with gross total resection, because one out of two patients develops disease recurrence at five years. Factors able to predict the risk of recurrence may be useful in selecting patients who require adjuvant treatment. In this study, we analyzed the molecular alterations of 22 atypical meningiomas undergoing complete surgical resection and their statistical correlation with the risk of recurrence. The loss of one copy of chromosome 18q and the loss of both copies of CDKN2A/B gene were significantly associated with a shorter time to recurrence. Therefore, we suggest that atypical meningiomas could be tested routinely for these genetic alterations to identify cases for adjuvant treatment. ABSTRACT: The use of adjuvant therapy is controversial in atypical meningiomas with gross total resection. Predictors of recurrence risk could be useful in selecting patients for additional treatments. The aim of this study was to investigate whether molecular features are associated with recurrence risk of atypical meningiomas. According to WHO classification, the diagnosis of atypical meningioma was based on the presence of one major criteria (mitotic activity, brain invasion) or three or more minor criteria. The molecular profile of 22 cases (eight mitotically active, eight brain-invasive, and six with minor criteria) was assessed exploring the mutational status and copy number variation of 409 genes using next generation sequencing. Of the 22 patients with a median follow up of 53.5 months, 13 had recurrence of disease within 68 months. NF2 mutation was the only recurrent alteration (11/22) and was unrelated to clinical-pathological features. Recurring meningiomas featured a significantly higher proportion of copy number losses than non-recurring ones (p = 0.027). Chromosome 18q heterozygous loss or CDKN2A/B homozygous deletion was significantly associated with shorter recurrence-free survival (p = 0.008; hazard ratio: 5.3). Atypical meningiomas could be tested routinely for these genetic alterations to identify cases for adjuvant treatment.