Project HOPE: The Pediatric/AYA Omics Project

项目摘要 儿童、青少年和年轻成人（AYA）以及成人的高级别胶质瘤（HGG/GBM） 人群代表了一种常见的未满足的治疗需求，其基础是细胞异质性， 这些肿瘤及其对治疗抵抗和残留疾病的贡献， 死亡尽管在这个年龄范围内进行了许多分子研究，但高级别胶质瘤和 胶质母细胞瘤复发的特征仍然很差，尽管是大多数临床 审判该项目利用多机构样本队列，解决有限的可用性 配对纵向患者标本的队列，并将这些队列与最先进的单细胞 通过复发分析成人和儿童胶质瘤的平台。希望工程团队包括：（1） Dana Farber癌症研究所：单细胞基因组学和分析（Mariella Filbin）;（2）UCSF：单细胞 基因组学和分析（Aaron迪亚兹）;（3）斯坦福大学：组织获取（Michelle Monje）;（4）CHOP： 组织采购（Adam Resnick）;（5）数据共享和NCI CDRC和CCDI互操作性， 整合（CHOP：Adam Resnick）; K. Alfred Yung，MD，MD安德森 癌症中心我们提出以下目标：目标1 -癌症的单细胞多组学测序 儿童和AYA高级别胶质瘤中的细胞。目的2 -非免疫细胞的单核测序 儿童和AYA高级别胶质瘤的微环境。目标3 -数据共享和数据共享。 总的来说，通过利用这一独特的单细胞多组学工具包为第三年的希望，并整合我们的 研究结果与项目关怀，我们将提供新的见解，发展，遗传，TME， 细胞状态的表观遗传驱动因素是HGG进化和对现有疗法耐药性的基础 在所有年龄组。

PROJECT SUMMARY High grade gliomas (HGG/GBM) across pediatric, adolescent and young adult (AYA), and adult populations represent a common unmet therapeutic need underpinned by the cellular heterogeneity of these tumors and its contribution to treatment resistance and residual disease, the ultimate cause of death. Despite numerous molecular studies across this age spectrum, high grade glioma and glioblastoma at recurrence remain poorly characterized, despite being the context for most clinical trials. This project leverages multi-institutional specimen cohorts that addresses the limited availability of paired longitudinal patient specimens and combines such cohorts with state-of-the-art single-cell platforms to profile adult and pediatric gliomas through recurrence. Project HOPE team consists of: (1) Dana Farber Cancer Institute: single cell genomics and analyses (Mariella Filbin); (2) UCSF: single cell genomics and analyses (Aaron Diaz); (3) Stanford: tissue procurement (Michelle Monje); (4) CHOP: tissue procurement (Adam Resnick); (5) Data Commons and NCI CDRC and CCDI interoperability and integration (CHOP: Adam Resnick); (6) Project Coordinator: W. K. Alfred Yung, MD, MD Anderson Cancer Center. We propose the following aims: Aim 1 - Single cell multi-omic sequencing of cancer cells in pediatric and AYA high-grade gliomas. Aim 2 - Single nucleus sequencing of the non-immune microenvironment of pediatric and AYA high-grade gliomas. Aim 3 - Data Commons and Data Sharing. Overall, by leveraging this unique single-cell multi-omics toolkit for Year 3 of HOPE, and integrating our findings with project CARE, we will provide novel insights into developmental, genetic, TME, and epigenetic drivers of cellular states that underlie HGG evolution and resistance to existing therapies across all age groups.