Biospecimen Unit

生物样本单元

• 批准号: 10259735
• 负责人: BRUCE E. JOHNSON
• 金额: $ 57.56万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-24 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10259735
• 关键词: Address; Anatomy; Archives; Atlases; Biological Assay; Biopsy; Boston; Breast biopsy; CDK4 gene; Cell Nucleus; Cells; Clinic; Clinical; Clinical Data; Clinical Research; Collaborations; Communication; Dana-Farber Cancer Institute; Data; Data Analyses; Data Set; Development; Dissociation; Ecosystem; Excision; Frozen Sections; Generations; Genomics; Geography; Goals; Histopathology; Human; Human Resources; Immunotherapy; Infrastructure; Laboratories; Large Intestine Carcinoma; Lead; Link; Location; Malignant - descriptor; Malignant Neoplasms; Maps; Measurement; Measures; Metastatic Melanoma; Microsatellite Repeats; Modality; Molecular; Non-Malignant; Operative Surgical Procedures; Pathologic; Pathology Report; Patient Outcomes Assessments; Patients; Process; Proteins; Quality Control; RNA; Research; Research Design; Research Personnel; Resistance; Sampling; Schedule; Secure; Services; Small Nuclear RNA; Solid Neoplasm; Space Perception; Stains; System; Tissues; Training; Treatment outcome; Vertebral column; adaptive learning; base; experience; genomic data; immune checkpoint blockade; malignant breast neoplasm; melanoma; operation; refractory cancer; single-cell RNA sequencing; success; therapy resistant; transcriptome sequencing; treatment response; tumor; tumor progression

Most patients who die from cancer do so because their cancer is resistant to available therapies. Tumors are comprised of diverse multicellular ecosystem that include malignant and non-malignant cells. Changes in the cellular state, spatial organization and interaction between subsets of cells in that ecosystem are likely to be central to cancer progression and therapeutic resistance, but invisible by bulk analyses. Thus, there is urgent need to chart an atlas of the cells that compose a tumor, their spatial organization and functional relationships and how those features differ in tumors that are resistant to therapy. The Boston Human Tumor Atlas Network Research Center (HTA-RC) will create three comprehensive atlases of the cellular geography of human cancer to understand how changes in the tumor ecosystem lead to therapeutic resistance. The atlases will chart the dynamic changes associated with resistance to targeted and immune-based therapies in: (1) Primary and acquired resistance to CDK4/6 inhibition in breast cancer; (2) Primary and acquired resistance to immune checkpoint blockade in metastatic melanoma; and (3) Primary resistance to immunotherapy in microsatellite stable (MSS) colorectal carcinoma (CRC) compared with microsatellite instable (MSI) CRC. To enable these goals, the Biospecimens Unit (BSU) will provide a comprehensive, rigorous, and nimble sample acquisition platform that provides the bridge between the clinic and a set of state-of-the-art cellular and spatial analytic assays that will form data backbone for the atlases. It will provide at least 100 clinically and pathologically annotated samples/year to the Molecular Characterization Unit (MCU) in a manner adequate for three downstream measurement modalities: (1) histopathology, based on H&E stains and pathology reports; (2) spatial multiplex RNA and protein data (by MERFISH, IHC, CODEX, and MIBI); and (3) single-cell genomics data, especially single cell and single nucleus RNA-Seq (scRNA-seq, snRNA-Seq). The proposed studies build on an established, tight local collaboration network that has already proven as a highly effective pioneer in generation of pilot-scale tumor atlas datasets. expand this infrastructure and the extensive experience within our clinical units to assure its success in the following aims: Aim 1: Collect biospecimens from resections and biopsies of breast cancer, melanoma and colorectal carcinoma. The BSU will identify, procure, and traffic samples from surgical suite to the laboratory. Aim 2: Conduct pre-analytic processing of biospecimens: The BSU will perform pre-analysic processing steps of biospecimens including tissue dissociation, snap freezing, sectioning for spatial analysis and archiving. Rigorous SOPs and quality control measures for each step already well-developed and employed routinely. Aim 3: Acquire and maintain clinical data associated with each sample: Accurate and comprehensive clinical pathological annotation will be linked to each sample, including careful assessment of the patients' outcomes.

大多数死于癌症的患者都是因为他们的癌症对现有疗法有抵抗力。肿瘤是 由多种多细胞生态系统组成，包括恶性和非恶性细胞。的变化 该生态系统中细胞状态、空间组织和细胞子集之间的相互作用可能是 对癌症进展和治疗耐药至关重要，但通过批量分析是看不见的。因此，迫切需要 需要绘制构成肿瘤的细胞图谱、它们的空间组织和功能关系 以及这些特征在对治疗有抵抗力的肿瘤中有何不同。波士顿人类肿瘤图谱网络 研究中心（HTA-RC）将创建三份人类细胞地理学综合图集 了解肿瘤生态系统的变化如何导致治疗耐药性。地图集 将绘制与靶向和免疫疗法耐药性相关的动态变化：(1) 乳腺癌对 CDK4/6 抑制的原发性和获得性耐药； (2) 原发性和获得性耐药 转移性黑色素瘤中的免疫检查点阻断； (3) 对免疫治疗的原发性耐药 微卫星稳定 (MSS) 结直肠癌 (CRC) 与微卫星不稳定 (MSI) CRC 的比较。到 为了实现这些目标，生物样本单位 (BSU) 将提供全面、严格且灵活的样本 采集平台，在诊所和一组最先进的细胞和空间之间架起桥梁 分析测定将构成地图集的数据主干。它将提供至少100个临床和病理学信息 每年向分子表征单元 (MCU) 注释样品，其方式足以容纳三个 下游测量方式：（1）组织病理学，基于H&E染色和病理报告； (2) 空间多重 RNA 和蛋白质数据（通过 MERFISH、IHC、CODEX 和 MIBI）； (3)单细胞基因组学 数据，尤其是单细胞和单核 RNA-Seq（scRNA-seq、snRNA-Seq）。拟议的研究建立 建立在一个已建立的、紧密的本地协作网络上，该网络已被证明是 生成中试规模的肿瘤图谱数据集。扩大这一基础设施和丰富的经验 我们的临床单位确保其成功实现以下目标： 目标 1：从切除物中收集生物样本 以及乳腺癌、黑色素瘤和结直肠癌的活检。 BSU 将确定、采购和 将样本从手术室运送到实验室。目标 2：进行预分析处理 生物样本：BSU 将执行生物样本（包括组织）的预分析处理步骤 解离、速冻、切片以进行空间分析和存档。严格的SOP和质量控制 每个步骤的措施都已制定完善并常规采用。目标 3：获得并维持临床 与每个样本相关的数据：将链接准确、全面的临床病理注释 每个样本，包括仔细评估患者的结果。