Molecular Pathology Research Unit, Virgen de la Salud Hospital, Toledo, Spain.
J Neuropathol Exp Neurol. 2012 Oct;71(10):882-93. doi: 10.1097/NEN.0b013e31826bf704.
Meningiomas are the most common primary brain tumors; they arise from the coverings of the brain. Although meningiomas are generally benign, some are more clinically aggressive, as reflected by their histopathological features or by their unexpected recurrence. We hypothesized that recurrent histologically benign meningiomas might have genetic features in common with those showing a more aggressive histology. By comparing gene expression profiles associated with meningioma progression and recurrence in 128 tumor samples (i.e. 83 benign World Health Organization [WHO] Grade I, 37 atypical WHO Grade II, and 8 anaplastic WHO Grade III) from 121 patients, we identified a 49-gene signature of meningioma aggressivity. This signature classified the tumors into 2 groups showing different clinical and pathological behaviors. The signature was composed of genes involved in the cell cycle (TMEM30B, CKS2, and UCHL1) and other pathways previously described as being altered in meningiomas, that is, WNT (SFRP1 and SFRP4) and transforming growth factor-β pathways (LTBP2 and LMO4). Overall, gene downregulation was observed in advanced and recurrent samples versus benign and original ones. We propose that this gene repression may be caused by gene promoter hypermethylation, as in the case of UCHL1 and SFRP1, suggesting that this epigenetic event, together with loss of specific chromosomal regions, may play an important role in meningioma progression and recurrence.
脑膜瘤是最常见的原发性脑肿瘤；它们起源于大脑的覆盖物。虽然脑膜瘤通常是良性的，但有些脑膜瘤具有更高的临床侵袭性，这反映在其组织病理学特征或意外复发中。我们假设，复发性组织学良性脑膜瘤可能具有与表现出更具侵袭性组织学特征的脑膜瘤相似的遗传特征。通过比较 128 个肿瘤样本（即 83 个良性世界卫生组织[WHO]I 级、37 个非典型 WHO II 级和 8 个间变性 WHO III 级）的基因表达谱与 121 例患者的进展和复发相关，我们确定了脑膜瘤侵袭性的 49 个基因特征。该特征将肿瘤分为两组，表现出不同的临床和病理行为。该特征由涉及细胞周期的基因（TMEM30B、CKS2 和 UCHL1）和其他先前描述为在脑膜瘤中改变的途径组成，即 WNT（SFRP1 和 SFRP4）和转化生长因子-β途径（LTBP2 和 LMO4）。总体而言，在高级和复发性样本中观察到基因下调，而在良性和原始样本中未观察到。我们提出，这种基因抑制可能是由于基因启动子的过度甲基化引起的，如 UCHL1 和 SFRP1 所示，这表明这种表观遗传事件，以及特定染色体区域的丢失，可能在脑膜瘤的进展和复发中发挥重要作用。
