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 National Cancer Institute（NCI）的癌症基因组学中心（CCG）成立于2011年，其使命是领导NCI的努力，以生成对人类肿瘤中所见的重要数据集，协调数据统一和共享努力的改动，并支持我们对大型数据的理解，并支持分析工具和计算方法的开发，旨在提高我们对大型数据的理解。 CCG还具有开发和应用尖端的基因组科学以预防癌症和更好地治疗癌症患者的目标，例如在NCI支持的临床试验的背景下。目前，一些大规模的癌症基因组研究项目属于CCG伞，其中包括由癌症基因组图集（TCGA）计划办公室和癌症基因组学办公室（OCG）管理的伞。 癌症基因组图集（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）发起了一项合作，以追求一个为期3年的试点项目，以确定更全面地分类与少数不同人类癌症相关的基因组变化的可行性。试点项目主要集中在三种肿瘤类型上：多形胶质母细胞瘤，卵巢的浆液性膀胱癌和肺鳞状癌。在接下来的4年中，试点项目扩展到大约30种肿瘤类型，截至2013年，大约有1 botabyte（Pb）的数据超过6,000例人类癌症。迄今为止的数据分析表明，可以通过将基因组分析中的潜水员信息与肿瘤生物学和临床数据相结合，并且可以有效且具有成本效益进行测序，从而确定与癌症相关的基因和基因组区域。 TCGA的强度是使用适当数量的样品提供统计上强大的结果，在发现新的癌症干预措施时为新时代设定了阶段。综合分析导致了对潜在抗性机制的意外假设的公式，精确地突出了这种项目设计的价值和功能，证明了大型样本同类人群的无偏见和系统的癌症基因组分析如何导致重要发现。 Biospecimen Core Resources（BCR） TCGA项目BCR充当集中组织加工中心，并为该程序提供了生物分子。此外，BCR还收集并标准化临床注释。标准运营方案（SOP）控制了临床数据收集，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对癌症基因组表征中心和基因组测序中心的生物分子分布。 BCR确保TCGA根据适当的人类受试者进行审查和知情同意的样本和数据，并且还代表了该项目的NIH政策。 TCGA计划的主要先决条件是获得高质量的生物测量。为了满足这一需求，NCI建立了一个临床站点网络，为集中质量控制和加工设施提供了高质量的临床注释生物测量。该设施是TCGA程序与为程序提供样品的组织源位点之间的主要接口。 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.,知识产权限制）。 TCGA项目管理选择建立集中组织加工模型，以确保将过程变量最小化，直到它们对分子分析结果的影响得到充分了解。该集中化特别意味着使用SOP在BCR处进行所有TCGA研究的组织和数据的所有操作。方差的最小化是指生物测量收据，后勤和物理管理的过程，处理分析物（来自组织等组织的分子提取物，例如DNA和RNA），组织的细分，最终的组织或分析物或分析物在所有中间和最终产物的QC的研究地点分布到研究地点。