Bolouri Hamid, Zhao Lue Ping, Holland Eric C
Division of Human Biology, and Solid Tumor and Translational Research, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA 98109;
Division of Public Health Sciences, FHCRC, Seattle, WA 98109;
Proc Natl Acad Sci U S A. 2016 May 10;113(19):5394-9. doi: 10.1073/pnas.1601591113. Epub 2016 Apr 26.
We show that visualizing large molecular and clinical datasets enables discovery of molecularly defined categories of highly similar patients. We generated a series of linked 2D sample similarity plots using genome-wide single nucleotide alterations (SNAs), copy number alterations (CNAs), DNA methylation, and RNA expression data. Applying this approach to the combined glioblastoma (GBM) and lower grade glioma (LGG) The Cancer Genome Atlas datasets, we find that combined CNA/SNA data divide gliomas into three highly distinct molecular groups. The mutations commonly used in clinical evaluation of these tumors are regionally distributed in these plots. One of the three groups is a mixture of GBM and LGG that shows similar methylation and survival characteristics to GBM. Altogether, our approach identifies eight molecularly defined glioma groups with distinct sequence/expression/methylation profiles. Importantly, we show that regionally clustered samples are enriched for specific drug targets.
我们表明,对大型分子和临床数据集进行可视化分析能够发现分子定义的高度相似患者类别。我们使用全基因组单核苷酸改变(SNA)、拷贝数改变(CNA)、DNA甲基化和RNA表达数据生成了一系列相互关联的二维样本相似性图。将此方法应用于胶质母细胞瘤(GBM)和低级别胶质瘤(LGG)的联合癌症基因组图谱数据集时,我们发现CNA/SNA联合数据将胶质瘤分为三个高度不同的分子组。这些肿瘤临床评估中常用的突变在这些图中呈区域分布。三个组中的一组是GBM和LGG的混合物,其甲基化和生存特征与GBM相似。总之,我们的方法识别出了八个具有不同序列/表达/甲基化谱的分子定义的胶质瘤组。重要的是,我们表明区域聚类的样本富含特定的药物靶点。