Abstract：
Meningioma (MN) is an important cause of disability, and predictive tools for estimating the risk of recurrence are still scarce. The need for objective and cost-effective techniques addressed to this purpose is well known. In this study, we present methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) as a friendly method for deepening the understanding of the mechanisms underlying meningioma progression. A large follow-up allowed us to obtain 50 samples, which included the primary tumor of 20 patients in which half of them are suffering one recurrence and the other half are suffering more than one. We histologically characterized the samples and performed MS-MLPA assays validated by FISH to assess their copy number alterations (CNA) and epigenetic status. Interestingly, we determined the increase in tumor instability with higher values of CNA during the progression accompanied by an increase in epigenetic damage. We also found a loss of HIC1 and the hypermethylation of CDKN2B and PTEN as independent prognostic markers. Comparison between grade 1 and higher primary MN\'s self-evolution pointed to a central role of GSTP1 in the first stages of the disease. Finally, a high rate of alterations in genes that are related to apoptosis and autophagy, such as DAPK1, PARK2, BCL2, FHIT, or VHL, underlines an important influence on cell-death programs through different pathways.
摘要：
脑膜瘤(MN)是致残的重要原因,估计复发风险的预测工具仍然很少。为此目的需要客观和成本有效的技术是众所周知的。在这项研究中,我们提出了甲基化特异性多重连接依赖性探针扩增(MS-MLPA)作为加深对脑膜瘤进展机制理解的友好方法.大规模的随访使我们获得了50个样本，其中包括20名患者的原发性肿瘤，其中一半患有一次复发，另一半患有一次以上。我们对样品进行了组织学表征，并进行了通过FISH验证的MS-MLPA测定，以评估其拷贝数改变（CNA）和表观遗传状态。有趣的是,我们确定了肿瘤不稳定性的增加,在进展过程中CNA的值较高,伴随着表观遗传损伤的增加.我们还发现HIC1的缺失以及CDKN2B和PTEN的高甲基化是独立的预后标志物。1级和较高原发性MN的自我进化之间的比较表明GSTP1在疾病的第一阶段中起着重要作用。最后,与细胞凋亡和自噬相关的基因改变率很高，如DAPK1，PARK2，BCL2，FHIT，或VHL，强调了通过不同途径对细胞死亡程序的重要影响。
