Abstract 2725: Establishment of the primary human tumor xenograft (tumorgraft) mouse model of pancreatic ductal adenocarcinoma.

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer continues to be plagued by a low overall 5 year survival rate, which has remained at a stagnant 5% over the past 30 years. In addition, pancreatic cancer is the 10th leading diagnosed cancer, yet is the 4th leading cause of cancer related deaths in the US, in both men and women. Recent research efforts have been focused on increasing our understanding of the molecular and genetic aspects of pancreatic cancer, in order to improve outcome for these patients. A major tool of pancreatic cancer research has been the use of established cancer cell lines, although the inherent ability of these cell lines to recapitulate human pancreatic disease is not ideal, due to growth in artificial environment and homogenous nature. Implantation of primary human tumor samples into immune compromised mice have been shown to be more genetically heterogeneous, and allow for more relevant genetic profiling data when compared to established cell lines. To better understand the molecular and genetic events in pancreatic cancer, we established a patient derived primary human tumor xenograft (tumorgraft) model system. Briefly, non-diagnostic tumor tissue was procured from previously consented patients at the University of Alabama at Birmingham Hospital, under IRB approved protocols. The tumors were then examined grossly by a pathologist, and immediately implanted into the flank of immune compromised mice. Here we report, a set of 10 PDAC tumors, with a mean age of patients at diagnosis of 68.3 (± 11.6) years. Primarily, these tumors were stage II (six IIA and four IIB) and with a histological grade reported as five moderately differentiated and five poorly differentiated. Lymph node involvement at the time of surgical resection was also assessed and six patients were positive, while four patients were negative. The tumorgrafts retained the morphological and histological characteristics of the primary tumor, even after serial passage in mice, as determined by a pathologist blinded to tumor identity. Currently, we are using next generation sequencing to generate detailed gene expression, epigenetic, and genotyping profiles of these established PDAC tumors. This work is supported by UAB/UMN SPORE in Pancreatic Cancer-Career Development Award and the Department of Pharmacology/Toxicology, UAB. Citation Format: Patrick L. Garcia, Tracy Gamblin, Leona N. Council, John D. Christein, Martin J. Heslin, Joseph Richardson, Karina J. Yoon. Establishment of the primary human tumor xenograft (tumorgraft) mouse model of pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2725. doi:10.1158/1538-7445.AM2013-2725