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Oncotarget. 2016 Sep 20;7(38):62533-62546. doi: 10.18632/oncotarget.11530.

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

Author information

1
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Korea.
2
Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, Korea.
3
Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.
4
Department of Chemistry, Seoul National University, Seoul, Korea.
5
Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
6
Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
7
Department of Pathology, Asan Medical Center, Seoul, Korea.
8
Department of Surgery, Asan Medical Center, Seoul, Korea.
9
Department of Physiology, University of Ulsan College of Medicine, Seoul, Korea.

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.

KEYWORDS:

cancer panel; heterogeneity; pancreatic cancer; patient-derived xenograft; single nucleotide polymorphism

PMID:
27613834
PMCID:
PMC5308744
DOI:
10.18632/oncotarget.11530
[Indexed for MEDLINE]
Free PMC Article

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