Genetic and metabolic comparison of orthotopic and heterotopic patient-derived pancreatic-cancer xenografts to the original patient tumors
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Eunsung Jun1,2, Seung-Mo Hong3, Hyun Ju Yoo4, Moon-Bo Kim5, Ji Sun Won1, Soyeon An3, In Kyong Shim6, Suhwan Chang2, Robert M. Hoffman7,8 and Song Cheol Kim1
1Division of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
2Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea
3Department of Pathology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
4Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
5MetaBio Inc., Gangdong-Gu, Seoul, South Korea
6Asan Institute for Life Science, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea
7Department of Surgery, University of California, San Diego, CA, USA
8AntiCancer Inc., San Diego, CA, USA
Song Cheol Kim, email: firstname.lastname@example.org
Robert M. Hoffman, email: email@example.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
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.
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