Biospecimen Repository Core

项目概要/摘要 生物标本库核心旨在为以下基础转化研究工作提供支持： 膀胱癌的治疗方法核心将在收集、注释、存储、分发、 以及跟踪来自生物样本库中登记的患者的尿路上皮癌生物样本（组织、尿液和血液 银行和治疗研究协议。详细的生物标本注释，包括预处理文件 分析处理变量、病理学发现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， 对所有同意接受尿路上皮癌生物标本材料的患者进行标准化纵向随访 仓库。Core还将为SPORE研究人员提供肿瘤的专家组织病理学评估 样本均来自研究方案中登记的患者和异种移植模型。核心也将 在执行和解释免疫组织化学和原位杂交检测方面提供帮助， 选择用于显微切割的组织并构建阵列。鉴于其形态上的显著异质性 膀胱癌，这些服务需要的专业知识超出了MSK病理核心可以提供， 强调核心主任的作用和投入的重要性。该核心的具体目标是： 具体目标1。为了维护和扩大一个模型尿路上皮癌资源，旨在收集，注释， 储存、处理和分发用于转化性尿路上皮癌研究的生物标本。 具体目标2。对所有人类和动物生物标本进行系统病理学评价， 制备适当的生物标本供SPORE研究者使用。 每个研究项目都广泛依赖于生物标本库核心，以实现其 翻译研究目标。对于RP-1，核心将有助于对以下物质进行前瞻性分子表征： 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的样品，以鉴定顺铂敏感性的新生物标志物， 尿液样本进行无细胞DNA分析。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，以确定基因，当突变时， 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、全外显子组测序 (WES)、RNAseq、TCRseq、免疫SEQ和MDSC定量），目的是鉴定预测性的 免疫检查点阻断反应的生物标志物。对于RP-4，生物样本库核心将 协助表征用于研究新型卡介苗菌株的异种移植模型 (BCG)并分析来自尿路上皮癌患者的样本，以鉴定 对BCG免疫疗法的反应。

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.