Project HOPE: The Pediatric/AYA Omics Project

项目总结 儿童、青少年和青壮年(Aya)和成人的高级别胶质瘤(HGG/GBM) 群体代表一个共同的未得到满足的治疗需求，其基础是细胞的异质性 这些肿瘤及其对治疗耐药和残留疾病的贡献，是 死亡。尽管对这一年龄段进行了大量的分子研究，但高级别胶质瘤和 复发的胶质母细胞瘤的特征仍然很差，尽管大多数临床情况都是这样。 审判。该项目利用多机构样本队列来解决可获得性有限的问题 将成对的纵向患者样本与最先进的单细胞相结合 通过复发来描述成人和儿童胶质瘤的平台。希望工程团队由以下人员组成：(1) Dana Farber癌症研究所：单细胞基因组学和分析(Mariella Filbin)；(2)加州大学旧金山分校：单细胞 基因组学与分析(Aaron Diaz)；(3)斯坦福：组织采购(Michelle Monje)；(4)CHOP： 组织采购(Adam Resnick)；(5)数据共享和NCI CDRC和CCDI的互操作性以及 整合(CHOP：Adam Resnick)；(6)项目协调员：W.K.Alfred Yung，医学博士，医学博士安德森 癌症中心。我们提出了以下目标：目标1--癌症的单细胞多基因组测序 儿童和AYA高级别胶质瘤中的细胞。目的2-非免疫的单核细胞测序 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。 总体而言，通过利用这一独特的单细胞多组学工具包用于希望的第三年，并将我们的 通过项目关怀，我们将提供对发育、遗传、TME和 细胞状态的表观遗传驱动因素是HGG进化和对现有治疗耐药的基础 所有年龄段的人。

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.