CORE C BIOSPECIMEN AND PATHOLOGY – PROJECT SUMMARY The Biospecimen and Pathology Core (Core C) will be responsible for accessioning and processing new biospecimens with annotated clinical data to provide the needed biospecimens for the four SPORE translational research projects, for the Developmental Research and Career Enhancement Programs, and for other investigators engaged in hepatobiliary cancer research. Core C will build on the existing International Hepatobiliary Neoplasia Registry and Biorepository, which has been coordinated by Dr. Lewis Roberts since 2001, and collaborate with additional existing biorepositories including the Genetics of Cholestatic Liver Diseases Registry, coordinated by Dr. Konstantinos Lazaridis, the Liver Transplant Registry coordinated by Dr. Kymberly Watt, and the Hepatobiliary Neoplasia Patient Derived Xenograft program which is jointly coordinated by Dr. Mark Truty and Dr. Roberts. Core C will also coordinate with The Fibrolamellar Hepatocellular Carcinoma Biorepository at the Rockefeller University under Dr. Sanford Simon, which will become part of the Core infrastructure. Core C will provide sample accessioning and pathology support for the early phase clinical trials as needed in the SPORE projects. Core C will coordinate with the Mayo Clinic Cancer Center Biospecimen Accessioning and Processing (BAP) Shared Resource to process blood samples to genomic DNA and serum and plasma aliquots, and with the Pathology Research Core (PRC) Shared Resource to provide histology and other tissue-based services, including paraffin and frozen sectioning, immunohistochemistry, tissue microarray (TMA) construction, and digital imaging. Requests for biospecimens will be reviewed by the Biospecimen Access Committee for Hepatobiliary Cancers (BAC-HEP), with priority access for SPORE investigators and consideration given primarily to scientific merit and availability of biospecimens. Input from the Biostatistics and Bioinformatics Core will be included in the evaluation of biospecimen requests. Dr. Torbenson will provide detailed annotation of the SPORE's tissue database for frozen and formalin-fixed paraffin-embedded tissues of all available patients who have had surgical resections for hepatobiliary cancer at Mayo Clinic, as well as for PDXs, a number of which are derived from percutaneous biopsies of patients with intermediate to advanced unresectable and metastatic disease. The availability of PDXs from biopsies of more advanced tumors will help to address the concern that most of the genetic and molecular analyses of liver and biliary tumors performed thus far, including for example, within The Cancer Genome Atlas project (TCGA), has been performed on early stage surgically resected tumors, not on the intermediate to advanced and metastatic stage tumors for which advances in therapy are urgently needed. Dr. Torbenson will also interpret IHC staining and provide other pathology support such as evaluating tumor samples from Sleeping Beauty, transgenic or knockout mouse models of liver and biliary cancer.

CORE C BIOSPECIMEN AND PATHOLOGY – PROJECT NARRATIVE The ability to carefully study the molecular and genetic characteristics of cancer tissues and correlate these features with clinical characteristics, response to therapy, and outcomes of patients with these cancers is critical to the development of improved strategies for prevention, early detection, diagnosis, and treatment of liver and biliary cancers. The Biospecimen and Pathology Core is therefore a critical resource for basic, translational and clinical research in liver and biliary cancers. Mayo Clinic already has one of the largest biospecimen repositories for liver and biliary cancers worldwide, but funding limitations have prevented us from fully achieving the scope of sample and data acquisition that would be possible with a fully funded biorepository. In addition, we have developed and are expanding an extensive network of national and international collaborators that will allow even more powerful studies of liver and biliary cancers in future years.