Biospecimen Unit

生物样本单元

• 批准号: 10902520
• 负责人: BRUCE E. JOHNSON
• 金额: $ 124.11万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-04 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10902520
• 关键词: Address; Anatomy; Archives; Atlases; Biological Assay; Biopsy; Boston; Breast biopsy; CDK4 gene; Cells; Clinic; Clinical; Clinical Data; Collaborations; Communication; Dana-Farber Cancer Institute; Data; Data Analyses; Data Set; Development; Dissociation; Ecosystem; Excision; Freezing; 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 Instability; 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; Solid Neoplasm; Space Perception; Stains; System; Tissues; Training; Treatment outcome; Vertebral column; adaptive learning; experience; genomic data; immune checkpoint blockade; malignant breast neoplasm; melanoma; operation; refractory cancer; single nucleus RNA-sequencing; single-cell RNA sequencing; spatial integration; success; therapy resistant; 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这样做是因为他们的癌症对现有疗法具有抗药性。肿瘤是 由多种多样的多细胞生态系统组成，包括恶性和非恶性细胞。变化 细胞状态、空间组织和生态系统中细胞亚群之间的相互作用可能是 对癌症进展和治疗抗性至关重要，但通过批量分析不可见。因此，迫切需要 我需要绘制一张组成肿瘤的细胞图谱，包括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的不同。波士顿人类肿瘤图谱网络 研究中心（HTA-RC）将创建三个人类细胞地理学的综合地图集。 了解肿瘤生态系统的变化如何导致治疗耐药性。的图谱 将绘制与靶向和基于免疫的治疗的耐药性相关的动态变化：（1） 乳腺癌中对CDK 4/6抑制的原发性和获得性耐药;（2）原发性和获得性耐药 转移性黑色素瘤中免疫检查点阻断;和（3）转移性黑色素瘤中对免疫疗法的原发性抗性 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，生物标本单位（BSU）将提供一个全面、严格和灵活的样本 采集平台，为诊所和一套最先进的细胞和空间 分析化验，将形成数据骨干的地图集。它将提供至少100个临床和病理 注释样品/年，以足以满足三个 下游测量模式：（1）组织病理学，基于H&E染色和病理学报告;（2） 空间多重RNA和蛋白质数据（通过MERFISH、IHC、CODEX和MIBI）;和（3）单细胞基因组学 数据，特别是单细胞和单核RNA-Seq（scRNA-seq，snRNA-Seq）。拟议的研究建立 建立了一个紧密的本地合作网络，该网络已被证明是 中试规模肿瘤图谱数据集的生成。扩大这一基础设施和丰富的经验， 我们的临床单位，以确保其在以下目标的成功：目标1：收集生物标本从切除 以及乳腺癌、黑色素瘤和结肠直肠癌的活组织检查。BSU将确定、采购和 把手术室的样本送到实验室目标2：进行分析前处理 生物标本：BSU将执行生物标本（包括组织）的分析前处理步骤 分离、速冻、切片以进行空间分析和存档。严格的SOP和质量控制 每一步的措施都已经制定好，并经常采用。目标3：获取和维护临床 与每个样本相关的数据：将链接准确和全面的临床病理学注释 包括仔细评估患者的结果。