Abstract B118: Developing a molecular and cellular atlas of pancreatic disease

Abstract

Abstract Experimental results generated from human pancreatic ductal adenocarcinoma (PDAC) specimens have produced a broad knowledge of pancreatic tumors. However, successful personalized treatment of pancreatic disease will require an exceptionally deep knowledge of the molecular and cellular diversity of tumors, as well as their evolution through the course of disease progression, therapeutics, relapse, and terminal disease burden. To address this need, we have conducted diverse but complementary experimental analyses on adjacent regions of fresh tumor specimens collected from over 70 primary pancreas specimens obtained during Whipple and RAMPS procedures. Coordination between surgical and research teams has ensured that only a minimum time elapses between surgical resection and specimen processing, thus limiting potential degradation by pancreatic enzymes. Researchers with diverse cancer biology expertise obtain adjacent dissections from three regions (i.e., tumor, dysplastic, and normal) within each pancreas specimen. An annotated image of the whole pancreas specimen records the location of each dissected portion relative to one another. Fresh tissues are immediately used to 1) characterize the phenotypic diversity of tumor and non-tumor cells in the microenvironment, 2) isolate and culture cancer stem cells, 3) perform high resolution imaging including 3D-SEM, 4) “bioprint” and culture three-dimensional, multi-cell-type structures, and 5) propagate tumors in mouse avatars. Genomics, epigenomics, and transcriptomics analyses are also performed on laser-captured specimens. In addition to primary PDAC tumors, other fresh pancreatic cancer specimens are being added to the collection including core needle biopsies obtained from treatment-naïve patients, metastases removed during primary tumor resection or recurrence, and tumor specimens from a rapid autopsy program. Importantly, all specimens are fully clinically annotated as patients are followed through the course of their disease. By comprehensively characterizing individual pancreatic tumors from many patients we hope to produce a unique body of information – an “Atlas” of pancreatic disease – that will inform the research community of new molecular and cellular features that contribute to the progression and therapeutic resistance of this devastating disease. Research data and clinical information in the Atlas will be accessible through a user-friendly customizable database. We hope that this resource will support the development of molecularly targeted early detection, therapeutics, and prevention in order to improve patient care. Funding for this initiative comes from philanthropic support to the Brenden-Colson Center for Pancreatic Care at Oregon Health and Science University. Citation Format: Jason M. Link, Brittany Allen-Petersen, Andrew Gunderson, Danielle Jorgens, Craig Dorrell, Jody Hooper, Philip Streeter, Markus Grompe, Lisa Coussens, Joe Gray, Hope Hardaker, Charles D. Lopez, Rosalie C. Sears, Brett C. Sheppard. Developing a molecular and cellular atlas of pancreatic disease. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B118.