Oncotarget

Research Papers:

Generation and molecular characterization of pancreatic cancer patient-derived xenografts reveals their heterologous nature

Jaeyun Jung, Cue Hyunkyu Lee, Hyang Sook Seol, Yeon Sook Choi, Eunji Kim, Eun Ji Lee, Je-Keun Rhee, Shree Ram Singh, Eun Sung Jun, Buhm Han, Seung Mo Hong, Song Cheol Kim _ and Suhwan Chang

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Oncotarget. 2016; 7:62533-62546. https://doi.org/10.18632/oncotarget.11530

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Abstract

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

Correspondence to:

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

ABSTRACT

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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