Generation and molecular characterization of pancreatic cancer patient-derived xenografts reveals their heterologous nature
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Jaeyun Jung1,*, Cue Hyunkyu Lee3,*, Hyang Sook Seol4, Yeon Sook Choi4, Eunji Kim3,5, Eun Ji Lee1, Je-Keun Rhee6, Shree Ram Singh7, Eun Sung Jun1, Buhm Han3, Seung Mo Hong8, Song Cheol Kim9, Suhwan Chang1,2
1Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Korea
2Department of Physiology, University of Ulsan College of Medicine, Seoul, Korea
3Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, Korea
4Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea
5Department of Chemistry, Seoul National University, Seoul, Korea
6Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Korea
7Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA
8Department of Pathology, Asan Medical Center, Seoul, Korea
9Department of Surgery, Asan Medical Center, Seoul, Korea
*These authors have contributed equally to this work
Song Cheol Kim, email: [email protected]
Suhwan Chang, email: [email protected]
Keywords: pancreatic cancer, patient-derived xenograft, single nucleotide polymorphism, cancer panel, heterogeneity
Received: June 01, 2016 Accepted: August 08, 2016 Published: August 23, 2016
Pancreatic ductal adenocarcinoma (PDAC) is the most challenging type of cancer to treat, with a 5-year survival rate of <10%. Furthermore, because of the large portion of the inoperable cases, it is difficult to obtain specimens to study the biology of the tumors. Therefore, a patient-derived xenograft (PDX) model is an attractive option for preserving and expanding these tumors for translational research. Here we report the generation and characterization of 20 PDX models of PDAC. The success rate of the initial graft was 74% and most tumors were re-transplantable. Histological analysis of the PDXs and primary tumors revealed a conserved expression pattern of p53 and SMAD4; an exome single nucleotide polymorphism (SNP) array and Comprehensive Cancer Panel showed that PDXs retained over 94% of cancer-associated variants. In addition, Polyphen2 and the Sorting Intolerant from Tolerant (SIFT) prediction identified 623 variants among the functional SNPs, highlighting the heterologous nature of pancreatic PDXs; an analysis of 409 tumor suppressor genes and oncogenes in Comprehensive Cancer Panel revealed heterologous cancer gene mutation profiles for each PDX-primary tumor pair. Altogether, we expect these PDX models are a promising platform for screening novel therapeutic agents and diagnostic markers for the detection and eradication of PDAC.
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