Department of Pathology, University of Valencia, 46010 Valencia, Spain.
Department of Pathology, Hospital General Universitario Valencia, 46014 Valencia, Spain.
Cells. 2020 Nov 6;9(11):2429. doi: 10.3390/cells9112429.
Glioblastoma multiforme (GB) is one of the most aggressive tumors. Despite continuous efforts to improve its clinical management, there is still no strategy to avoid a rapid and fatal outcome. amplification is the most characteristic alteration of these tumors. Although effective therapy against it has not yet been found in GB, it may be central to classifying patients. We investigated somatic-copy number alterations (SCNA) by multiplex ligation-dependent probe amplification in a series of 137 GB, together with the detection of vIII and FISH analysis for amplification. Publicly available data from 604 patients were used as a validation cohort. We found statistical associations between amplification and/or vIII, and SCNA in and . Interestingly, we found that both vIII and losses on were independent markers of bad prognosis ( = 0.028 and 0.014, respectively). Finally, we got an unsupervised hierarchical classification that differentiated three clusters of patients based on their genetic alterations. It offered a landscape of co-alterations that may improve the comprehension of the mechanisms underlying GB aggressiveness. Our findings can help in defining different genetic profiles, which is necessary to develop new and different approaches in the management of our patients.
胶质母细胞瘤(GB)是最具侵袭性的肿瘤之一。尽管不断努力改善其临床管理,但仍然没有策略可以避免快速和致命的结局。扩增是这些肿瘤最典型的改变。尽管在 GB 中尚未发现针对它的有效治疗方法,但它可能是对患者进行分类的核心。我们通过多重连接依赖性探针扩增在一系列 137 例 GB 中研究了体细胞拷贝数改变(SCNA),并检测了扩增的 vIII 和 FISH 分析。使用来自 604 名患者的公开可用数据作为验证队列。我们发现扩增和/或 vIII 与 和 之间存在统计学关联。有趣的是,我们发现 vIII 和 缺失都是预后不良的独立标志物(分别为 = 0.028 和 0.014)。最后,我们得到了一种无监督的层次分类,根据患者的遗传改变将其分为三个亚群。它提供了一个 共改变的景观,这可能有助于深入了解 GB 侵袭性的机制。我们的发现可以帮助确定不同的遗传特征,这对于制定我们患者管理的新方法和不同方法是必要的。