BCR Support for the NCI TCGA Program

BCR 对 NCI TCGA 计划的支持

• 批准号: 8757478
• 负责人: DAVID HEIMBROOK
• 金额: $ 440万
• 依托单位: LEIDOS BIOMEDICAL RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-26 至 2018-09-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8757478
• 关键词: Amendment; Animals; Archives; Biopsy Specimen; Cancer Intervention; Cancer Patient; Cataloging; Catalogs; Characteristics; Clinical; Clinical Data; Clinical Trials; Collaborations; Collection; Computer software; Contracts; DNA; Data; Data Analyses; Data Collection; Data Coordinating Center; Data Set; Databases; Development; Diagnostic; Documentation; Drug Formulations; Drug or chemical Tissue Distribution; Enrollment; Ensure; Formalin; Genes; Genome; Genomics; Glioblastoma; Goals; Guidelines; Histology; Human; Informatics; Informed Consent; Institutional Review Boards; Intellectual Property; Laboratories; Lead; Logistics; Lung; Malignant Neoplasms; Microscopy; Mission; Modeling; Molecular; Monitor; National Cancer Institute; National Human Genome Research Institute; Nucleic Acids; Office of Cancer Genomics; Ovary; Paraffin Embedding; Pathology; Performance; Pilot Projects; Policies; Procedures; Process; Property; Proteins; Proteomics; Protocols documentation; Quality Control; RNA; Reporting; Research; Research Infrastructure; Research Project Grants; Resources; Sample Size; Sampling; Scanning; Science; Serous Cystadenocarcinoma; Shipping; Ships; Site; Slide; Source; Specimen; Squamous cell carcinoma; Staging; Task Performances; The Cancer Genome Atlas; Time; Tissue Banking; Tissue Banks; Tissue Extracts; Tissue Sample; Tissues; Tumor Biology; United States National Institutes of Health; Work; analytical tool; cancer genome; cancer genomics; clinical research site; cohort; cost; data acquisition; design; falls; follow-up; genome sequencing; human subject; improved; material transfer agreement; meetings; operation; outreach; prevent; programs; resistance mechanism; sample collection; tissue processing; tumor; virtual; working group

Background The Center for Cancer Genomics (CCG) at the National Cancer Institute (NCI) was established in 2011 with a mission to lead the NCI efforts in generating critical datasets required to catalog the alterations seen in human tumors, coordinating data unification and sharing efforts, and supporting development of analytical tools and computational approaches aimed at improving our understanding of the large-scale, multidimensional data. CCG also has the goal of developing and applying cutting-edge genomic science to prevent cancer and better treat cancer patients, for example in the context of NCI-supported clinical trials. Currently, several large-scale cancer genome research projects fall under the CCG umbrella including those managed by The Cancer Genome Atlas (TCGA) Program Office and the Office of Cancer Genomics (OCG). The Cancer Genome Atlas (TCGA) Program In 2006, the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) initiated a collaboration to pursue a 3-year pilot project to determine the feasibility of more comprehensively cataloging the genomic alterations associated with a small number of different human cancers. The pilot project focused mainly on three tumor types: glioblastoma multiforme, serous cystadenocarcinoma of the ovary, and squamous carcinoma of the lung. The pilot project expanded to approximately 30 additional tumor types over the next 4 years and as of 2013 represents approximately 1 petabyte (PB) of data on over 6,000 cases of human cancer. Data analysis to date demonstrates that cancer-associated genes and genomic regions can be identified by combining diverse information from genome analyses with tumor biology and clinical data, and that the sequencing of selected regions can be conducted efficiently and cost-effectively. The strength of TCGA is to produce unprecedented multi-dimensional data sets using an appropriate number of samples to provide statistically robust results that sets the stage for a new era in the discovery of new cancer interventions. The integrative analyses leading to the formulation of an unanticipated hypothesis on a potential mechanism of resistance highlights precisely the value and power of such project design, demonstrating how unbiased and systematic cancer genome analyses of large sample cohorts can lead to important discoveries. Biospecimen Core Resource (BCR) The TCGA Project BCR serves as a centralized tissue processing center and provides the biomolecules for the Program. In addition, the BCR collects and standardizes clinical annotations. Standard Operating Protocols (SOP) governed clinical data collection, sample collection, pathological examination, biomolecule (e.g., DNA and RNA) extractions, quality control, laboratory data collection, and biomolecule distribution to the Cancer Genome Characterization Centers and the Genome Sequencing Centers. The BCR ensures that samples and data were received by TCGA under appropriate human subjects review and informed consent, and also that Material Transfer Agreements represented the policies of the NIH for this project. A major prerequisite of the TCGA Program was the acquisition of high quality biospecimens. To meet this need, NCI established a network of clinical sites providing high quality, clinically annotated biospecimens to a centralized quality control and processing facility. This facility is the primary interface between the TCGA program and the Tissue Source Sites that provide samples to the program. It must be noted that the term ¿high quality¿ refers not only to the histological and molecular properties of the tissue, but also to characteristics such as degree and quality of clinical annotation, the existence of appropriate informed consent provisions for the intended use of the biomolecules and data, collection and subsequent distribution to TCGA under an Institutional Review Board (IRB) reviewed protocol, as well as unencumbered access for research use (e.g., intellectual property restrictions). TCGA project management chose to establish a centralized tissue processing model to ensure that process variables are minimized until their effects on the results of molecular analyses become well understood. This centralization specifically means that all operations to process tissue and data for any single cancer studied by TCGA occur at the BCR, utilizing SOPs. This minimization of variance refers to the processes of biospecimen receipt, logistical and physical management, processing into analytes (the molecular extracts from tissue such as DNA and RNA), the subdivision of tissue, and finally distribution of tissue or analytes to the research sites with rigorous QC of all intermediate and final products along the workflow.

背景 美国国家癌症研究所 (NCI) 的癌症基因组学中心 (CCG) 成立于 2011 年，其使命是领导 NCI 生成编目人类肿瘤变化所需的关键数据集、协调数据统一和共享工作，以及支持分析工具和计算方法的开发，以提高我们对大规模多维数据的理解。 CCG 的目标还包括开发和应用尖端基因组科学来预防癌症并更好地治疗癌症患者，例如在 NCI 支持的临床试验中。目前，CCG 旗下有多个大型癌症基因组研究项目，包括由癌症基因组图谱 (TCGA) 项目办公室和癌症基因组学办公室 (OCG) 管理的项目。 癌症基因组图谱 (TCGA) 计划 2006 年，美国国家癌症研究所 (NCI) 和国家人类基因组研究所 (NHGRI) 启动了一项为期 3 年的试点项目，以确定更全面地对与少数不同人类癌症相关的基因组改变进行编目的可行性。该试点项目主要关注三种肿瘤类型：多形性胶质母细胞瘤、卵巢浆液性囊腺癌和肺鳞状细胞癌。该试点项目在接下来的 4 年内扩展到​​大约 30 种其他肿瘤类型，截至 2013 年，包含超过 6,000 例人类癌症病例的大约 1 PB 数据。迄今为止的数据分析表明，通过将基因组分析的各种信息与肿瘤生物学和临床数据相结合，可以识别癌症相关基因和基因组区域，并且可以高效且经济高效地对选定区域进行测序。 TCGA 的优势在于使用适当数量的样本生成前所未有的多维数据集，以提供统计上稳健的结果，为发现新癌症干预措施的新时代奠定基础。综合分析导致对潜在耐药机制提出了意想不到的假设，这恰恰突出了此类项目设计的价值和力量，展示了对大样本队列进行公正和系统的癌症基因组分析如何能够带来重要的发现。 生物样本核心资源 (BCR) TCGA 项目 BCR 充当集中组织处理中心，并为该计划提供生物分子。此外，BCR 还收集临床注释并对其进行标准化。标准操作协议 (SOP) 管理临床数据收集、样本收集、病理检查、生物分子（例如 DNA 和 RNA）提取、质量控制、实验室数据收集以及向癌症基因组表征中心和基因组测序中心分发生物分子。 BCR 确保 TCGA 在适当的人类受试者审查和知情同意下收到样本和数据，并且材料转让协议代表 NIH 对于该项目的政策。 TCGA 计划的一个主要先决条件是获取高质量的生物样本。为了满足这一需求，NCI 建立了一个临床站点网络，为集中的质量控制和处理设施提供高质量、有临床注释的生物样本。该设施是 TCGA 计划和为该计划提供样本的组织源站点之间的主要接口。必须指出的是，术语“高质量”不仅指组织的组织学和分子特性，还指诸如临床注释的程度和质量、生物分子和数据的预期用途是否存在适当的知情同意条款、根据机构审查委员会 (IRB) 审查的协议收集和随后分发给 TCGA 等特征，以及研究用途的无阻碍访问（例如， 知识产权限制）。 TCGA 项目管理层选择建立集中式组织处理模型，以确保最小化过程变量，直到充分了解它们对分子分析结果的影响。这种集中化具体意味着处理 TCGA 研究的任何单一癌症的组织和数据的所有操作都在 BCR 上利用 SOP 进行。这种差异最小化是指生物样本接收、后勤和物理管理、加工成分析物（从组织中提取的分子提取物，如 DNA 和 RNA）、组织细分以及最终将组织或分析物分配到研究地点的过程，并对整个工作流程中的所有中间产品和最终产品进行严格的质量控制。