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死于癌症，是因为他们的癌症对现有的治疗方法具有抵抗力。肿瘤是 由不同的多细胞生态系统组成，其中包括恶性和非恶性细胞。的变化 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 癌症进展和治疗耐药的中心，但通过大量分析看不到。因此，有一个紧迫的问题 需要绘制组成肿瘤的细胞、它们的空间组织和功能关系的图谱 以及这些特征在抵抗治疗的肿瘤中有何不同。波士顿人类肿瘤地图集网络 研究中心(HTA-RC)将创建三个全面的人类细胞地理学地图集 了解肿瘤生态系统的变化是如何导致治疗抵抗的。地图集 将绘制与靶向和基于免疫的治疗耐药性相关的动态变化图表：(1) 乳腺癌对CDK4/6抑制的原发和获得性耐药；(2)对 转移性黑色素瘤的免疫检查点阻断；以及(3)对免疫治疗的主要抵抗 微卫星稳定(MSS)结直肠癌(CRC)与微卫星不稳定(MSI)结直肠癌的比较。至 为了实现这些目标，生物谱系单位(BSU)将提供全面、严格和灵活的样本 采集平台，为临床和一套最先进的细胞和空间 将构成地图集数据主干的分析分析。它将在临床和病理上提供至少100个 分子表征单元(MCU)的注解样本/年 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(由MerFish、IHC、Codex和MIBI提供)；以及(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)。建议的研究建立 在成熟、紧密的本地协作网络上，该网络已证明是 生成中试规模的肿瘤图谱数据集。扩展此基础设施以及其中的广泛经验 我们的临床单位确保其在以下目标上取得成功：目标1：从切除中收集生物标本 以及乳腺癌、黑色素瘤和结直肠癌的活检。BSU将识别、采购和 从手术室到实验室的交通样本。目标2：进行分析前处理 生物样品：BSU将对包括组织在内的生物样品进行分析前处理步骤 解离、快速冻结、切片以进行空间分析和存档。严格的标准操作规程和质量控制 每一步的措施都已经制定得很好，并经常使用。目标3：获取和维护临床应用 与每个样本相关的数据：将链接准确和全面的临床病理注释 对每个样本，包括仔细评估患者的结果。