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2013 Scientific Report

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VARI | 2013 Research Interests Biospecimen science uses evidence-based approaches to study the effects of collection, processing, and storage on the biological parameters of biospecimens in an effort to establish best practices for the collection and control of high-quality human biospecimens for research. In our Program for Biospecimen Science (PBS), two broad categories of interest are the pre- and post-analytical variables that can alter in vivo biological assessments. Model systems are used for the study of the variables that can arise in biospecimen management, and we are working to establish in vitro and in vivo tissue models that can be used to answer specific questions. Laboratory of Analytical Pathology The Laboratory of Analytical Pathology, directed by Galen Hostetter, M.D., provides histology and morphometric analysis using immunohistochemistry, in situ hybridization, tissue microarray technology, digital imaging and analysis by light and spectral microscopy, confocal microscopy, and diagnostic tissue evaluation. The lab can visualize cells and their components with striking clarity, and the images enable researchers to determine where in a cell particular molecules are located and to quantify the molecules through imaging analysis software. See p. 28 for a complete description. Laboratory of Microarray Technology The Laboratory of Microarray Technology is directed by Sok Kean Khoo, Ph.D. It provides gene expression arrays, miRNA arrays, and array CGH using the Agilent microarray platform and cDNA platform capabilities. Microarray technology plays an important part in the discovery of genetic signatures, copy number variations, and biomarkers. Genomic DNA or total RNA from a wide range of tissues, including blood and fresh or frozen tissues, can be analyzed. Agilent microarrays in array formats from 4 x 44,000 to 1 x 1 million are used, and whole-genome gene expression (GE) arrays, exon arrays, miRNA arrays, and array CGH are available. Human, mouse, rat, and canine arrays are most frequently processed, but the lab offers GE and custom arrays for more than 20 plant and animal model organisms. Recently the lab has successfully developed a microarray gene expression technique for RNA from newborn blood spots. This technique can detect thousands of gene signatures using low-resolution arrays, enabling clinical research into the origins, epidemiology, and diagnosis of pediatric diseases. Cytogenetics Core facility Julie Koeman, CG (ASCP), directs the Cytogenetics Core facility, which uses both cytogenetic and molecular genetic techniques to identify structural and numerical chromosomal aberrations associated with mammalian disease. Information about the loss or gain of a gene or about gene amplification can be generated from many sample types, and that information can be used to validate microarray data. Cytogenetic techniques can also be used for species identification, which is especially valuable when working with tumor xenograft models. The cytogenetic services include fluorescence in situ hybridization (FISH), custom FISH probe production, spectral karyotyping (SKY), transgene localization, routine karyotyping (G-banding), chromosomal breakage studies, and mouse embryonic stem cell trisomy 8 screening. Biorepository services Dan Rohrer directs the operations of the biorepository, including database tracking and management of biospecimen inventory; biospecimen kit development and manufacturing; shipping and tracking services; procurement of surgical tissue and biospecimens from patient populations; quality control assessment of operations for the collection and banking of biospecimens; and biospecimen project management. The VARI biorepository contains approximately 2,000 frozen human tissues and a paraffin block archive of human diagnostic tissues currently exceeding 800,000 blocks. Tissue acquisition is in collaboration with West Michigan hospitals, providing fresh-frozen and paraffin-embedded surgical tissues and blood from consenting patients. The biorepository is designed to provide human tumors to investigators with IRB-approved basic and translational research projects. 31

Van Andel Research Institute | Scientific Report Comprehensive biospecimen resource for the NCI Cancer Human Biobank The Cancer Human Biobank (caHUB) includes biospecimen source sites, a comprehensive biospecimen resource, a pathology resource center, and a comprehensive data resource to implement the collection and management of high-quality biospecimens for NCI and NIH projects such as the Genotype-Tissue Expression (GTEx) program. VARI’s Program for Biospecimen Science was awarded funding as the comprehensive biospecimen resource for the caHUB. Using a stringent quality management program and project-specific standard operating procedures, we produce biospecimen kits for the collection and management of human tissues and pathology services for caHUB projects. In 2011 and 2012, our Program was awarded major contracts to support the caHUB projects. Biospecimen resource for the Multiple Myeloma Research Foundation CoMMpass study The Multiple Myeloma Research Foundation launched a genomics study, CoMMpass SM , in collaboration with the Translational Genomics Research Institute (TGen), our Program for Biospecimen Science, and Spectrum Health Medical Center. The primary aim of CoMMpass is to collect biospecimens from 1,000 multiple myeloma patients for genomic analysis to assess changes associated with major clinical events, treatment response, and disease progression. This data will fuel therapeutic target discovery, drug development, and biomarker validation. Biospecimen kits are designed by the VARI PBS for the collection of bone marrow aspirate and peripheral blood. The kits, which are tracked from design through shipment and use, maintain biospecimens at 2–8 °C during shipment to Spectrum, where they are characterized by flow cytometry and BRAF sequencing in a clinical diagnostic laboratory. The PBS isolates CD138 + tumor cells and nucleic acids from patient samples for molecular sequencing and analysis at TGen. CoMMpass biospecimen management includes kit design, distribution, tracking, processing, and biobanking. Since July 2011, 200 patient cases have been processed, of which 28 have completed full genomic analysis. In 2011 the PBS was awarded an eight-year contract for this project. Recent Publications Jewell, Scott D. 2012. Perspective on biorepository return of results and incidental findings. Minnesota Journal of Law, Science and Technology 13(2): 655–667. Resau, James H., Nhan T. Ho, Karl Dykema, Matthew S. Faber, Julia V. Busik, Radoslav Z. Nickolov, Kyle A. Furge, Nigel Paneth, Scott Jewell, and Sok Kean Khoo. 2012. Evaluation of sex-specific gene expression in archived dried blood spots (DBS). International Journal of Molecular Sciences 13(8): 9599–9608. Glaser, Ronald, Rebecca Andridge, Eric V. Yang, Arwa Y. Shana’ah, Michael Di Gregorio, Min Chen, Sheri L. Johnson, Lawrence A. De Renne, David R. Lambert, Scott D. Jewell, et al. 2011. Tumor site immune markers associated with risk for subsequent basal cell carcinomas. PLoS One 6(9): e25160. Moore, Helen M., Andrea Kelly, Scott D. Jewell, Lisa M. McShane, Douglas P. Clark, Renata Greenspan, Pierre Hainaut, Daniel F. Hayes, Paula Kim, Elizabeth Mansfield, et al. 2011. Biospecimen reporting for improved study quality. Biopreservation and Biobanking 9(1): 57–70. 32

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