Genetic and metabolic comparison of orthotopic and heterotopic patient-derived pancreatic-cancer xenografts to the original patient tumors

// Eunsung Jun 1, 2 , Seung-Mo Hong 3 , Hyun Ju Yoo 4 , Moon-Bo Kim 5 , Ji Sun Won 1 , Soyeon An 3 , In Kyong Shim 6 , Suhwan Chang 2 , Robert M. Hoffman 7, 8 and Song Cheol Kim 1 1 Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea 2 Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea 3 Department of Pathology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea 4 Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea 5 MetaBio Inc., Gangdong-Gu, Seoul, South Korea 6 Asan Institute for Life Science, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea 7 Department of Surgery, University of California, San Diego, CA, USA 8 AntiCancer Inc., San Diego, CA, USA Correspondence to: Song Cheol Kim, email: drksc@amc.seoul.kr Robert M. Hoffman, email: all@anticancer.com Keywords: pancreatic cancer; patient-derived orthotopic xenograft PDOX; patient-derived heterotopic xenograft PDHX; homology; heterogeneity Received: September 16, 2017      Accepted: October 13, 2017      Published: December 21, 2017 ABSTRACT Tumors from 25 patients with pancreatic cancer were used to establish two patient-derived xenograft (PDX) models: orthotopic PDX (PDOX) and heterotopic (subcutaneous) PDX (PDHX). We compared gene expression by immunohistochemistry, single-nucleotide polymorphism (SNP), DNA methylation, and metabolite levels. The 4 cases, of the total of 13 in which simultaneous PDHX & PDOX models were established, were randomly selected. The molecular-genetic characteristics of the patient’s tumor were well maintained in the two PDX models. SNP analysis demonstrated that both groups were more than 90% identical to the original patient’s tumor, and there was little difference between the two models. DNA methylation of most genes was similar among the two models and the original patients tumor, but some gene sets were hypermethylated the in PDOX model and hypomethylated in the PDHX model. Most of the metabolites had a similar pattern to those of the original patient tumor in both PDX tumor models, but some metabolites were more prominent in the PDOX and PDHX models. This is the first simultaneous molecular-genetic and metabolite comparison of patient tumors and their tumors established in PDOX and PDHX models. The results indicate high fidelity of these critical properties of the patient tumors in the two models.