Multi-Omic Profiling of Glioma Patient Tumors and Patient-Derived Model Systems

We have created a resource of transcriptomic (RNAseq), genomic (whole-exome seq), and lipidomic (untargeted shotgun) profiling data from over 175 molecularly diverse glioma tumors and derivative models in orthotopic mouse xenografts and gliomasphere cultures from over 110 unique patient tumor lines. Provided in this dataset are matched bulk RNA and whole-exome paired-end sequencing data from resected gliomas and derived model systems performed on Illumina HiSeq and NovaSeq sequencing instruments. This comprehensive dataset powers multiple studies aiming to derive molecular signatures of intertumoral heterogeneity and perturbation responses in glioma. Through integrative multi-omic analyses in Minami, et al., 2023, PMID: 37236196, we identified that CDKN2A deletion remodels the GBM lipidome and consequently primes CDKN2A-deleted tumors for ferroptosis. Lipidomics data related to this study are publicly available here. In another study, we used a combination of molecular profiling and functional profiling of apoptotic potential to stratify patients into groups with differential vulnerability to the current standard-of-care in gliomas, and in combination with drugs targeting intrinsic apoptosis, largely informed but not limited to TP53 mutation status.]]>

本研究构建了一套多组学谱学数据集，涵盖110余株独特患者来源肿瘤系的175余例分子特征多样的胶质瘤实体瘤，及其对应的原位小鼠异种移植模型与神经球培养衍生模型的转录组学（transcriptomic）、RNA测序（RNAseq）、基因组学（genomic）、全外显子组测序（whole-exome seq）及脂质组学（lipidomic）、非靶向鸟枪法（untargeted shotgun）谱学数据。本数据集包含切除胶质瘤标本及其衍生模型系统的匹配批量RNA测序与全外显子组双端测序数据，测序平台为Illumina HiSeq及NovaSeq测序仪。这套全面的数据集可支撑多项研究，用于解析胶质瘤的瘤间异质性分子特征与扰动响应模式。在Minami等人2023年的研究（PMID: 37236196）中，我们通过整合多组学分析发现，CDKN2A缺失会重塑胶质母细胞瘤（GBM）的脂质组，进而使CDKN2A缺失型肿瘤易于发生铁死亡（ferroptosis）。本研究相关的脂质组学数据已在此公开获取。在另一项研究中，我们结合分子谱学分析与凋亡潜能功能谱学分析，将胶质瘤患者分为不同亚组，这些亚组对当前胶质瘤标准治疗方案的敏感性存在差异；该分类方法主要基于但不限于TP53突变状态，同时联合靶向内源性凋亡的药物治疗策略。