Multidimensional scaling of diffuse gliomas: application to the 2016 World Health Organization classification system with prognostically relevant molecular subtype discovery.
Multidimensional scaling of diffuse gliomas: application to the 2016 World Health Organization classification system with prognostically relevant molecular subtype discovery.
复制标题
DOI：
10.1186/s40478-017-0443-7
复制
发表时间：
2017-05-22
影响因子：
7.1
通讯作者：
Holland EC
中科院分区：
文献类型：
--
作者：
Cimino PJ;Zager M;McFerrin L;Wirsching HG;Bolouri H;Hentschel B;von Deimling A;Jones D;Reifenberger G;Weller M;Holland EC
2016年世界卫生组织（WHO）对中枢神经系统（CNS）肿瘤分类的最新更新表明，通过将组织形态学特征与复发性分子改变相结合，首次有组织地重建脑肿瘤分类。修订后的CNS肿瘤诊断标准也试图减少观察者间组织学解释的差异，并提供与临床结局相关的更准确的分层。例如，弥漫性神经胶质瘤（WHO分级II-IV）现在根据异柠檬酸脱氢酶1或2（IDH）突变状态进行分子分层，WHO分级II和III的神经胶质瘤根据1 p/19 q共缺失状态进行亚分层。目前，弥漫性胶质瘤的分级仍然依赖于组织学参数。独立于WHO分类标准，来自癌症基因组图谱（TCGA）的弥漫性胶质瘤分子特征的多维尺度分析已经确定了不同的分子亚组，并允许其在二维（2D）空间中可视化。使用基于网络的平台Oncoscape作为工具，我们将多维缩放衍生的分子组应用于2016年WHO弥漫性胶质瘤分类的2D可视化。在这里，我们表明TCGA数据的分子多维尺度提供了代表2016年WHO弥漫性胶质瘤分类的2D聚类。此外，我们使用该平台成功地鉴定和定义了新的基于拷贝数改变的分子亚型，这些分子亚型独立于WHO分级，并可预测临床结果。使用德国胶质瘤网络前瞻性胶质母细胞瘤患者队列的独立数据集进一步验证了这些分子亚型的预后效用。本文的在线版本（doi：10.1186/s40478-017-0443-7）包含补充材料，可供授权用户使用。
Recent updating of the World Health Organization (WHO) classification of central nervous system (CNS) tumors in 2016 demonstrates the first organized effort to restructure brain tumor classification by incorporating histomorphologic features with recurrent molecular alterations. Revised CNS tumor diagnostic criteria also attempt to reduce interobserver variability of histological interpretation and provide more accurate stratification related to clinical outcome. As an example, diffuse gliomas (WHO grades II–IV) are now molecularly stratified based upon isocitrate dehydrogenase 1 or 2 (IDH) mutational status, with gliomas of WHO grades II and III being substratified according to 1p/19q codeletion status. For now, grading of diffuse gliomas is still dependent upon histological parameters. Independent of WHO classification criteria, multidimensional scaling analysis of molecular signatures for diffuse gliomas from The Cancer Genome Atlas (TCGA) has identified distinct molecular subgroups, and allows for their visualization in 2-dimensional (2D) space. Using the web-based platform Oncoscape as a tool, we applied multidimensional scaling-derived molecular groups to the 2D visualization of the 2016 WHO classification of diffuse gliomas. Here we show that molecular multidimensional scaling of TCGA data provides 2D clustering that represents the 2016 WHO classification of diffuse gliomas. Additionally, we used this platform to successfully identify and define novel copy-number alteration-based molecular subtypes, which are independent of WHO grading, as well as predictive of clinical outcome. The prognostic utility of these molecular subtypes was further validated using an independent data set of the German Glioma Network prospective glioblastoma patient cohort. The online version of this article (doi:10.1186/s40478-017-0443-7) contains supplementary material, which is available to authorized users.