A series of four core resources support these research projects and also establish a strong programmatic infrastructure for translational research in GI cancers.
Core A: Administration
The Administrative Core will provide for overall direction, coordination, and administration of the Case Gl SPORE, including oversight of the SPORE Executive Committee, SPORE Internal Advisory Board, SPORE External Advisory Board, and SPORE Patient Advocates Advisory Board.
Core B: Biospecimen
The Biospecimen Core will work closely with SPORE investigators to enhance their projects by supplying quality controlled colon and esophagus tissues and expert consultation regarding multiple aspects of pathology. A longstanding collaboration between members of the Biospecimen Core and individual project investigators has resulted in the compilation of an extensive tissue archive of cancers from 2,443 patients with primary colon cancers of known pathological state and data based clinical follow-up. A substantial archive of paraffin blocks of normal, pre-cancer and cancer specimen, including metastases of regional lymph nodes, distant organs and subsequent recurrences is maintained. Frozen material with matched normal controls from 887 of these cases is banked. There are 444 esophageal cancers and Barrett's esophagus paraffin specimens and 202 frozen esophageal specimens. Historically, the Core has supplied Gl SPORE investigators with microdissected esophageal and colon cancers suitable for analysis of the temporal sequence of gene mutations, colon cancer tissue arrays suitable for immunohistochemistry and in situ hybridization, frozen tissue suitable for RNA profiling, and blood specimens for genotyping in the discovery of novel inherited traits of colon cancer predisposition. The core also banks blood specimens for future biomarker development. Additionally the Core will: i) organize and distribute all prospective Gl biospecimen procedures to SPORE investigators; ii) provide access to its existing tissue archive resource; iii) identify tissues of interest from archive and prospective accrual to investigators; iv) manage biospecimens obtained by Individual projects for later targeted investigation; v) provide histopathological quality control for tissue sections with project specific morphology case reviews and oversee and provide longitudinal follow-up of clinical outcomes linked to these tissues; vi) provide tissue microarray sections for tissue targets of interest; and vii) provide expertise in immunohistochemistry assessment and samples appropriate for specific studies. The primary objective is to provide a resource that contributes significantly to individual project goals and cooperation between other Gl SPOREs.
Core C: Biostatistics
Director: Jill S. Barnholtz-Sloan, PhD
GI malignancies are a complex constellation of diseases, most likely caused by the complex interplay between genes and environmental factors; only a small proportion of these tumors are caused by a known germline mutation. Therefore, large-scale research projects, such as the ones proposed in this GI SPORE application, are necessary to have an impact on early detection, diagnosis and prevention. We will therefore develop a centralized Biostatistics Core infrastructure for data management, study design, and statistical analysis, to allow integration of data across all research projects and Cores within the SPORE. This Core will meet a broad assortment of requirements for both the SPORE as a whole and for each individual project and Core, leading to many scientific manuscripts and submission of additional grants and pilot projects.
The overall goal of the Biostatistics Core of the GI SPORE is to provide the necessary expertise and support in experimental design and biostatistics, genetic epidemiology and Illumina sequencing statistical analysis and interpretation, in order to promote and enhance the research projects and Cores. It will thus provide a Core service across all SPORE activities, enhancing and improving the quality of the research undertaken.
The Biostatistics Core is drawn from faculty and resources in the Biostatistics Shared Resource of the Case Comprehensive Cancer Center (CCCC) and the Department of Epidemiology and Biostatistics of Case Western Reserve University (CWRU) School of Medicine. We draw from resources being developed and supported by the CCCC in data management, informatics and Illumina sequencing analysis. Drs. Jill Barnholtz-Sloan and Robert Elston will co-direct this Core facility; both are members of the CCCC and the Department of Epidemiology and Biostatistics, Dr. Elston being currently the chair of the Department.
Aim 1: To provide statistical analysis consultation, expertise and resources to enhance discovery for gastrointestinal (GI) malignancies. The Core will assist investigators with all facets of statistical analysis and interpretation. Both established and novel, tailored analytic methods are available to promote scientific discovery for GI malignancies within the Core. The Core will facilitate access to existing CCCC informatics systems to link them with project specific databases, facilitating statistical analysis, discovery and collaboration.
Aim 2: To provide expertise required for the statistical analysis of Illumina sequencing data. The Core will provide the expertise necessary to appropriately analyze sequencing data through constant monitoring for, and comparison of, available techniques and so utilization of state-of-the-art techniques.
Core personnel will interact with SPORE investigators in all stages of research, from the formulation of the research questions, through experimental design, data management, data analysis (including outcomes analysis), interpretation, writing scientific manuscripts and grants, to dissemination of results. The Core has demonstrated expertise in development of novel approaches to the analysis of complex disease data. The Biostatistics Core will provide a natural foundation for cross-pollination among the projects, the Core personnel collaborating with all project investigators and Core directors