The Mayo GBM Xenograft National Resource

马约胶质母细胞瘤（GBM）异种移植国家资源将为用户提供强大的动物模型，具有相应的表型和分子表征，概括了来自79个患者来源的异种移植物（PDX）的人类GBM肿瘤的关键分子和组织学表型。这些肿瘤模型是在马约诊所通过将手术组织直接植入免疫功能低下的小鼠中，然后在小鼠中连续传代这些肿瘤来创建的。PDX模型高度代表人GBM肿瘤，并保留了其来源的人肿瘤的复杂分子特征。这些高度转化和相关的模型已被广泛用于神经肿瘤学研究;马约GBM PDX被用于100多篇同行评审的手稿，是37个NIH资助的赠款（包括16个NINDS资助的赠款）的关键试剂。作为对人类肿瘤样品上可用的丰富的多组学数据集的补充（例如，癌症基因组图谱），该R24的目标是在我们的GBM PDX模型中提供类似水平的分子表征，并使数据免费提供给用户。这个大型PDX面板的全面多组学数据的可用性至关重要，可以让用户轻松识别最相关的肿瘤模型，用于其特定的研究项目。为了实现这一目标，本研究中提出的RNAseq、总蛋白质组学和磷酸蛋白质组学研究（目标1）将与我们的全外显子组测序和全甲基化组研究相结合，以提供整个PDX组的广泛分子表征。这些数据集将使用系统生物学方法进行整合，以识别严重失调的信号网络，这将有助于生物信息学经验有限的用户解释多组学PDX表征（目标2）。我们将使用开源cBioPortal软件（用于在MSKCC托管癌症基因组图谱数据）托管所有PDX分子和表型表征，为具有强大的综合多组学搜索功能的强大数据库提供用户友好的界面（Aim 3）。与此同时，马约GBM异种移植国家资源将开发早期传代肿瘤分析物（DNA、RNA和蛋白质提取物）和冷冻或冷藏肿瘤样本的档案，以分发给用户（目标4）。通过这种方式，为该拟议国家资源计划的目标将显著提高高度特征化的GBM PDX模型的可用性，用于神经肿瘤学社区的基础和转化研究。

The Mayo Glioblastoma (GBM) Xenograft National Resource will provide users with robust animal models, with corresponding phenotypic and molecular characterizations, that recapitulate key molecular and histologic phenotypes of human GBM tumors from a panel of 79 patient-derived xenografts (PDX). These tumor models were created at the Mayo Clinic by implanting surgical tissue directly into immunocompromised mice and then serially passaging these tumors in mice. The PDX models are highly representative of human GBM tumors and preserve the complex molecular features of the human tumors they were derived from. These highly translational and relevant models have been used widely in neuro-oncology research; the Mayo GBM PDXs are used in over 100 peer-reviewed manuscripts and are key reagents in 37 NIH-funded grants (including 16 NINDS-funded grants). As a complement to the rich multi-omic data sets available on human tumor samples (e.g., The Cancer Genome Atlas), the goal of this R24 is to provide a similar level of molecular characterization across our GBM PDX models and make the data freely-available for Users. Availability of comprehensive multi-omic data for this large PDX panel is critically important to allow Users to readily identify the most relevant tumor model(s) for use in their specific research projects. Towards this goal, the RNAseq, total- and phospho-proteomics studies proposed in this study (Aim 1) will be combined with our whole-exome sequencing and whole methylome studies to provide a broad molecular characterization across the PDX panel. These datasets will be integrated using systems biology approaches to identify critically deregulated signaling networks, which will help Users with limited bioinformatics experience interpret the multi-omic PDX characterizations (Aim 2). We will host all of the PDX molecular and phenotypic characterizations using the open-source cBioPortal software (used to host The Cancer Genome Atlas data at MSKCC) to provide a user-friendly interface to a powerful database with robust integrative multi-omic search capabilities (Aim 3). In parallel, the Mayo GBM Xenograft National Resource will develop an archive of early-passage tumor analytes (DNA, RNA, and protein extracts) and frozen or cryopreserved tumor samples for distribution to Users (Aim 4). In this way, the Aims planned for this proposed National Resource will significantly enhance the availability of highly characterized GBM PDX models for use in basic and translational research across the neuro-oncology community.