BCR Support for the NCI TCGA Program

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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.