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 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努力生成对人类肿瘤中观察到的改变进行编目所需的关键数据集，协调数据统一和共享工作，并支持旨在提高我们对大规模多维数据的理解的分析工具和计算方法的开发。CCG的目标还包括开发和应用尖端的基因组科学来预防癌症和更好地治疗癌症患者，例如在NCI支持的临床试验中。目前，几个大规模的癌症基因组研究项目属于CCG的保护伞，包括由癌症基因组图谱（TCGA）计划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） 2006年，美国国家癌症研究所（NCI）和美国国家人类基因组研究所（NHGRI）发起了一项为期3年的试点项目，以确定更全面地编目与少数不同人类癌症相关的基因组改变的可行性。该试点项目主要侧重于三种肿瘤类型：多形性胶质母细胞瘤、卵巢浆液性囊腺癌和肺鳞状细胞癌。在接下来的4年里，该试点项目扩展到大约30种其他肿瘤类型，截至2013年，该项目代表了6,000多例人类癌症病例的约1 PB数据。迄今为止的数据分析表明，癌症相关基因和基因组区域可以通过将来自基因组分析的各种信息与肿瘤生物学和临床数据相结合来识别，并且可以有效且经济地进行选定区域的测序。 TCGA的优势在于使用适当数量的样本产生前所未有的多维数据集，以提供统计上稳健的结果，为发现新的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，这恰恰凸显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CCR作为一个集中的组织处理中心，为该计划提供生物分子。此外，BCR还收集和分析临床注释。标准操作规程（SOP）管理临床数据收集、样品收集、病理学检查、生物分子（例如，DNA和RNA）提取、质量控制、实验室数据收集和生物分子分配到癌症基因组表征中心和基因组测序中心。BCR确保TCGA在适当的人类受试者审查和知情同意的情况下接收样本和数据，并且材料转移协议代表NIH对该项目的政策。 TCGA计划的一个主要先决条件是获得高质量的生物标本。为了满足这一需求，NCI建立了一个临床研究中心网络，为集中质量控制和处理设施提供高质量的临床注释生物标本。该机构是TCGA项目与向该项目提供样本的组织来源研究中心之间的主要接口。必须指出的是，“高质量”一词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、是否存在针对生物分子和数据的预期用途的适当知情同意条款、根据机构审查委员会（IRB）审查的方案收集并随后分发给TCGA等特征，以及用于研究用途的不受限制的访问（例如，知识产权限制）。 TCGA项目管理层选择建立一个集中的组织处理模型，以确保过程变量最小化，直到它们对分子分析结果的影响得到充分理解。这种集中化特别意味着TCGA研究的任何单一癌症的组织和数据处理的所有操作都在BCR进行，使用SOP。这种差异最小化指的是生物样本接收、后勤和物理管理、加工成分析物（组织的分子提取物，如DNA和RNA）、组织细分以及最终将组织或分析物分配到研究中心的过程，其中所有中间和最终产品沿着工作流程进行严格的QC。