Biospecimen Repository Core

项目摘要/摘要 Biospecimen知识库核心旨在为以下项目的基础翻译研究工作提供支持 膀胱癌中的孢子。核心将在收集、注释、存储、分发、 以及追踪尿路上皮癌生物样本(组织、尿液和血液) 银行业务和治疗研究方案。详细的生物样品注释，包括预 分析处理变量、病理结果和患者临床病史信息将记录在 强大的关系数据库。我们将采取严格的数据质量保证和质量控制措施，以及 所有同意使用尿路上皮癌生物显微镜材料的患者的标准化纵向随访 存储库。该中心还将为孢子调查人员提供肿瘤组织病理学方面的专家评估 样本既来自参加研究方案的患者，也来自异种移植模型。核心还将 协助执行和解释免疫组织化学和原位杂交分析， 显微解剖组织的选择和阵列的构建。考虑到显著的形态异质性 对于膀胱癌，这些服务需要的专业知识超出了MSK病理核心所能提供的范围， 强调核心董事的作用和投入的重要性。核心的具体目标是： 具体目标1.维护和扩展尿路上皮癌模型资源，其设计用于收集、注释 储存、加工和分发用于转译尿路上皮癌研究的生物样品。 具体目标2.对所有人和动物的生物寄生虫进行系统的病理学评估 供孢子调查员使用的适当生物检验剂的制备。 每个研究项目都广泛地依赖于BioSpecimen知识库核心来实现其 翻译研究目标。对于RP-1，核心将有助于未来的分子表征 尿路上皮癌的DNA损伤反应基因突变并将有助于肿瘤的准备 用于全外显子组测序以识别顺铂敏感性的新生物标记物的样本以及与血液和 用于无细胞DNA分析的尿样。对于RP-2，核心将提供血液样本和匹配的肿瘤 下一代测序分析用于识别基因，当基因突变时，这些基因与增加的 患尿路上皮癌的遗传风险。对于RP-3，核心将为多平台提供血液和组织样本 分析(PD-L1免疫组织化学、T细胞克隆性、肿瘤突变负荷、整个外显子组测序 (WES)、RNAseq、TCRseq、免疫SEQ和MDSC定量)，目的是确定预测性 免疫检查点阻断反应的生物标志物。对于RP-4，Biospecimen库核心将 协助鉴定用于研究卡介苗新菌株的异种移植模型 (卡介苗)和尿路上皮癌患者样本的分析，以确定预测生物标志物 对卡介苗免疫治疗的反应。

PROJECT SUMMARY/ABSTRACT The Biospecimen Repository Core is designed to provide support to the basic translational research efforts of the SPORE in Bladder Cancer. The Core will play a central role in collecting, annotating, storing, distributing, and tracking urothelial cancer biospecimens (tissue, urine, and blood) from patients enrolled in biospecimen banking and therapeutic research protocols. Detailed biospecimen annotation, including documentation of pre- analytic processing variables, pathology findings, and patient clinical history information will be recorded in robust relational databases. We will conduct rigorous data quality assurance and quality control measures, and standardized longitudinal follow-up of all consented patients with materials in the urothelial cancer biospecimen repository. The Core will also provide SPORE investigators with expert histopathological evaluation of tumor samples both from patients enrolled on research protocols and from xenograft models. The Core will also provide assistance in performing and interpreting immunohistochemical and in situ hybridization assays, in selecting tissue for microdissection and construction of arrays. Given the significant morphologic heterogeneity of bladder cancers, these services require expertise beyond what MSK Pathology Core can provide, underscoring the importance of the role and input of the Core Directors. The specific aims of the core are: Specific Aim 1. To maintain and expand a model urothelial cancer resource designed to collect, annotate, store, process, and distribute biospecimens for translational urothelial cancer research. Specific Aim 2. To perform systematic pathologic evaluation of all human and animal biospecimens and preparation of appropriate biospecimens for use by SPORE investigators. Each of the research projects relies extensively on the Biospecimen Repository Core to achieve their translational research objectives. For RP-1, the core will aid with the prospective molecular characterization of urothelial cancers for mutations in DNA damage response genes and will assist with the preparation of tumor samples for whole-exome sequencing to identify novel biomarkers of cisplatin-sensitivity and with blood and urine samples for cell-free DNA analysis. For RP-2, the core will provide blood samples and matched tumor for next-generation sequencing analyses to identify genes, which when mutated are associated with increased inherited risk for urothelial cancer. For RP-3, the core will provide blood and tissue samples for multi-platform analyses (PD-L1 immunohistochemistry, T-cell clonality, tumor mutational load, whole exome sequencing (WES), RNAseq, TCRseq, immunoSEQ and MDSC quantitation) with the goal of identifying predictive biomarkers of response to immune checkpoint blockade. For RP-4, the Biospecimen Repository Core will assist in the characterization of xenograft models used to study novel strains of bacillus Calmette-Guérin (BCG) and with the analysis of samples from patients with urothelial cancer to identify predictive biomarkers of response to BCG immunotherapy.