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之所以这样做，是因为他们的癌症对可用疗法有抵抗力。肿瘤是 由包括恶性和非恶性细胞在内的多种多细胞生态系统组成。变化 细胞状态，空间组织以及该生态系统的细胞子集之间的相互作用可能为 癌症进展和治疗性抗性的核心，但可以通过大量分析看不见。因此，很紧急 需要绘制组成肿瘤，其空间组织和功能关系的细胞的地图集 以及这些特征在耐药性肿瘤上有何不同。波士顿人类肿瘤网络 研究中心（HTA-RC）将创建人类细胞地理的三个综合图像 癌症了解肿瘤生态系统的变化如何导致治疗性抗性。地图集 将绘制与抗靶向和免疫疗法的抗性相关的动态变化：（1） 乳腺癌中对CDK4/6抑制的主要和获得性的抗性； （2）主要和获得的抵抗力 转移性黑色素瘤中的免疫检查点阻滞； （3）对免疫疗法的主要抵抗 与微卫星（MSI）CRC相比，微卫星稳定（MSS）结直肠癌（CRC）。到 启用这些目标，生物测量单元（BSU）将提供全面，严格且敏捷的样本 采集平台可提供诊所与一组最先进的蜂窝和空间之间的桥梁 分析测定将形成用于地图集的数据主链。它将在临床和病理上至少提供100个 分子表征单元（MCU）的带注释样品以三个方式适合三个 下游测量方式：（1）基于H＆E染色和病理报告的组织病理学； （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 在一个既定，紧密的当地合作网络上，已被证明是一位非常有效的先驱 生成试验尺度肿瘤数据集。扩大此基础架构和丰富的经验 我们的临床单位确保其在以下目的中的成功：目标1：从切除术中收集生物测量 以及乳腺癌，黑色素瘤和结直肠癌的活检。 BSU将识别，采购和 从外科套件到实验室的交通样品。目标2：进行预分析的处理 生物测量：BSU将执行包括组织在内的生物测量的预生物处理步骤 解离，快照冻结，用于空间分析和存档的切片。严格的SOP和质量控制 每个步骤的措施已经发达和常规采用。目标3：获取和维持临床 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，包括对患者预后的仔细评估。