Abstract C46: Establishing a living biobank of patient-derived organoids of intraductal papillary mucinous neoplasms

Abstract

Pancreatic cancer is the third leading cause of cancer-related deaths in the United States. There is an unmet need to develop strategies to detect pancreatic cancer at an early, operable stage and prevent its progression. Intraductal papillary mucinous neoplasms (IPMNs) are cystic pancreatic cancer precursors that comprise nearly 50% of pancreatic cysts detected incidentally via computed tomography (CT) scans. Since IPMNs can progress from low- and moderate-grade dysplasia and invasion, the study of these lesions offers a prime opportunity to develop early detection and prevention strategies. Organoids are an ideal preclinical platform to study IPMNs, and the objective of the current investigation was to establish the first living biobank of IPMN tumor organoids. IPMN tumors and adjacent normal pancreatic tissues were harvested from 15 patients undergoing pancreatic surgical resection at Moffitt Cancer Center & Research Institute (Tampa, FL) between 2017 and 2019. Following immunohistopathologic analysis of primary tissues, organoid cultures were generated, expanded, and cryopreserved. Furthermore, organoid cultures were generated from cryopreserved tissues as well. Count and size of the organoids over time was determined via the Image-Pro Premier 3D Version digital platform. Genomic characterization of the organoids was performed through DNA fingerprinting, and a subset of cases were sequenced. The success rates of organoid generation from IPMN tumor and adjacent normal pancreatic tissues were 81% and 87%, respectively. IPMN organoids derived from different IPMN subtypes tissues showed different morphologies in vitro, with the low- and moderate-grade pancreatobiliary subtypes showing the highest proliferation rates. This model has potential to provide new opportunities to unveil mechanisms of IPMN progression to invasion and to shed insight into novel biomarkers for detection and targets for chemoprevention. Citation Format: Dayana Reverón, Francisca Beato, Gina DeNicola, Antonio Ortiz, Barbara Centeno, Kun Jiang, Daniel Jeong, Mokenge Malafa, Pamela Hodul, Kaleena Deszi, Jennifer Permuth, Jason Fleming. Establishing a living biobank of patient-derived organoids of intraductal papillary mucinous neoplasms [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C46.