Project Summary The aims of the Biospecimen and Pathology Resources (BPR) Core (Core B) are to facilitate the storage and distribution of comprehensively annotated, high-quality biospecimens and their derivatives, and to provide professional and technical pathology services to the principal investigators and collaborators of our SPORE and Kidney Cancer Program. All three SPORE projects utilize Core B, which is critical to achieving their aims. It is an indispensable component of our SPORE and leverages and expands (without duplicating) existing pathology resources in our National Cancer Institute (NCI)-designated Simmons Comprehensive Cancer Center. We deliver basic histology, immunohistochemistry (IHC), in situ hybridization (ISH), tissue microarrays, whole slide imaging, image analysis, and laser-capture microdissection services, and make available unique cancer tissue derivatives such as primary cancer cell cultures and cell lines, cryopreserved tissues, DNA, RNA, and patient- derived xenografts (PDX or tumorgrafts, TG). These efforts are complemented by several national initiatives led by the Core. This Core provides expertise in histomorphologic evaluation of human kidney tumors, human tumorgrafts in mice, kidney tumors in transgenic and knockout animal models, and in the interpretation of IHC and ISH and multiplex immunoassays. The BPR Core develops IHC and molecular assays and has experience in the deployment of CLIA-certified laboratory tests, such as our PD-L1 IHC. The BPR Core currently has fresh- frozen renal tumor and paired-normal kidney (or blood) tissues for >1,700 racially and ethnically diverse patients; a unique live-tissue repository of >1,900 kidney tumor tissues preserved viable in DMSO for mechanistic studies to address questions arising from genomic and other studies of inert tissues; >200 independent TG lines; 47 primary tumor cell lines representing a wide variety of tumors; and integrated genomic analyses (exome sequencing, RNA-Seq and SNP arrays) of >500 RCC patients. Specimen data is linked to the institutional tissue bank, and to comprehensive patient clinical data through Kidney Cancer Explorer (Core C). The BPR Core provides routine quality control for SPORE investigators to ensure that the tissues are optimal, and several of our protocols have been published in Nature Protocols and serve as benchmarks in the fields of tissue processing for integrated genomic analyses and TG utilization for preclinical drug testing. Our repository has had significant utilization, with >1,000 samples having been shipped to collaborators both internally, as well as externally. TGs have been extensively utilized to evaluate RCC drug sensitivity, study radiation responsiveness, explore tumor biomarkers, understand cancer biology (including rare syndromes), and dissect metabolic derangements in RCC. Studies with these tissues have been published in high-impact journals such as Nature Genetics, Nature Communications, and Lancet Oncology. ...