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努力生成所需的关键数据集，以记录人类肿瘤的变化，协调数据统一和共享努力，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的目标也是开发和应用尖端基因组科学来预防癌症和更好地治疗癌症患者，例如在NCI支持的临床试验的背景下。目前，几个大型癌症基因组研究项目属于CCG框架下，包括由癌症基因组图谱(TCGA)计划办公室和癌症基因组办公室(OCG)管理的项目。 癌症基因组图谱(TCGA)计划 2006年，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变化进行编目的可行性。试点项目主要集中在三种肿瘤类型：多形性胶质母细胞瘤、卵巢浆液性囊腺癌和肺鳞癌。该试点项目在接下来的4年中扩大到大约30种其他肿瘤类型，截至2013年，该项目代表了超过6,000例人类癌症病例的约1PB数据。到目前为止的数据分析表明，通过将基因组分析中的各种信息与肿瘤生物学和临床数据相结合，可以识别与癌症相关的基因和基因组区域，并且可以有效和经济地对选定区域进行测序。 TCGA的优势是使用适当数量的样本产生前所未有的多维数据集，以提供统计上可靠的结果，为发现新的癌症干预措施奠定新时代。导致对潜在耐药机制提出意想不到的假设的综合分析恰好突显了这种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导致重要发现。 生物医学核心资源(BCR) TCGA Project BCR是一个集中的组织处理中心，为该计划提供生物分子。此外，BCR还收集和标准化临床注释。标准操作规程(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生物分子向癌症基因组表征中心和基因组测序中心的分配。BCR确保TCGA在适当的人体受试者审查和知情同意下收到样本和数据，并确保材料转让协议代表国家卫生研究院对该项目的政策。 TCGA计划的一个主要前提是获得高质量的生物检疫菌种。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的临床注释生物标本。该设施是TCGA程序和为程序提供样本的组织源站点之间的主要接口。必须指出的是，“高质量”一词不仅指组织的组织学和分子属性，还指临床注释的程度和质量、对生物分子和数据的预期用途存在适当的知情同意条款、根据机构审查委员会(IRB)审查的协议收集并随后分发给TCGA，以及研究用途的无限制使用(例如，知识产权限制)。 TCGA项目管理部门选择建立一个集中的组织处理模型，以确保在充分了解过程变量对分子分析结果的影响之前，将过程变量降至最低。这种集中化明确地意味着，TCGA研究的任何单个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品的接收、后勤和物理管理、加工成分析物(从组织中提取的分子，如DNA和RNA)、组织细分，最后将组织或分析物分配到研究地点，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。