PURPOSE Assessment of the risk of recurrence is essential to determine the therapeutic strategy of meningioma treatment. Many relapsing or aggressive meningiomas show elevated mitotic and/or Ki67 indices, reflecting cell cycle deregulation. As CDKN2A is a key tumor suppressor gene involved in cell cycle control, we investigated whether CDKN2A alterations may be involved in tumor recurrence. METHODS We carried out a comparative analysis of 17 recurrent and 13 non-recurrent meningiomas. CDKN2A single nucleotide variations (SNVs), deletions, methylation status of the promotor, and p16 expression were investigated. Results were correlated with the recurrent or non-recurrent status and clinicopathological data. RESULTS We identified a CDKN2A SNV (NM_000077, exon2, c.G442A, p.Ala148Thr) in five meningiomas that was significantly associated with recurrence (p = 0.03). This mutation, confirmed by Sanger sequencing and referenced in the COSMIC database in various cancers, has not been reported in meningioma. The presence of one of the three following CDKN2A alterations-p.(Ala148Thr) mutation, whole homozygous or heterozygous gene loss, or promotor methylation > 8%-was observed in 13 of the 17 relapsing meningiomas and was strongly associated with recurrence (p < 0.0001) and a Ki67 labeling index > 7% (p = 0.004). CONCLUSION We report an undescribed p.(Ala148Thr) CDKN2A mutation in meningioma that was only present in relapsing tumors. In our series, CDKN2A gene alterations were only found in recurrent meningiomas. However, our results need to be evaluated on a larger series to ensure that these CDKN2A alterations can be used as biomarkers of recurrence in meningioma.

中文翻译：

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复发性和非复发性脑膜瘤CDKN2A基因改变的分析。

目的评估复发风险对于确定脑膜瘤治疗的治疗策略至关重要。许多复发性或侵袭性脑膜瘤显示有丝分裂和/或Ki67指数升高，反映了细胞周期失调。由于CDKN2A是参与细胞周期控制的关键肿瘤抑制基因，因此我们研究了CDKN2A改变是否可能与肿瘤复发有关。方法我们对17例复发性和13例非复发性脑膜瘤进行了比较分析。CDKN2A单核苷酸变异（SNVs），缺失，启动子的甲基化状态和p16表达进行了调查。结果与复发或非复发状态和临床病理数据相关。结果我们鉴定出CDKN2A SNV（NM_000077，exon2，c.G442A，p。在5个脑膜瘤中，Ala148Thr）与复发显着相关（p = 0.03）。该突变已通过Sanger测序确认，并已在COSMIC数据库中用于多种癌症中，但尚未在脑膜瘤中报道。在17例复发性脑膜瘤中的13例中观察到以下三个CDKN2A改变-p。（Ala148Thr）突变，全纯合或杂合基因缺失或启动子甲基化> 8％之一，并且与复发密切相关（p < 0.0001）和Ki67标记指数> 7％（p = 0.004）。结论我们报道了脑膜瘤中未描述的p。（Ala148Thr）CDKN2A突变，仅在复发性肿瘤中存在。在我们的系列中，仅在复发性脑膜瘤中发现了CDKN2A基因改变。然而，