Generation and molecular characterization of pancreatic cancer patient-derived xenografts reveals their heterologous nature.
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.
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Korea.
Jaeyun
J
Jung
Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, Korea.
Cue Hyunkyu
CH
Lee
Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.
Hyang Sook
HS
Seol
Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.
Yeon Sook
YS
Choi
Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, Korea.|Department of Chemistry, Seoul National University, Seoul, Korea.
Eunji
E
Kim
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Korea.
Eun Ji
EJ
Lee
Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Je-Keun
JK
Rhee
Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
Shree Ram
SR
Singh
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Korea.
Eun Sung
ES
Jun
Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul, Korea.
Buhm
B
Han
Department of Pathology, Asan Medical Center, Seoul, Korea.
Seung Mo
SM
Hong
Department of Surgery, Asan Medical Center, Seoul, Korea.
Song Cheol
SC
Kim
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, Korea.|Department of Physiology, University of Ulsan College of Medicine, Seoul, Korea.
Suhwan
S
Chang
D000818:Animals; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D059472:Exome; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D015999:Multivariate Analysis; D009154:Mutation; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D015398:Signal Transduction; D051901:Smad4 Protein / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
C497796:SMAD4 protein, human; D051901:Smad4 Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
cancer panel; heterogeneity; pancreatic cancer; patient-derived xenograft; single nucleotide polymorphism