title: Development and characterization of a colon PDX model that reproduces drug responsiveness and the mutation profiles of its original tumor.
abstract: Cultures of primary tumors are very useful as a personalized screening system for effective therapeutic options. We here describe an effective method of reproducing human primary colon tumors through primary culture and a mouse xenograft model. A total of 199 primary colon tumor cultures were successfully established under optimized conditions to enrich for tumor cells and to expand it for long-term storage in liquid nitrogen. To examine whether these stored cultures retained original tumor properties, fifty primary cultures were xenografted into NOD-SCID mouse. Histological and tumor marker analysis of four representative tumor xenografts revealed that all of the xenograft retained its primary tumor characteristics. Oncomap analysis further showed no change in the major mutations in the xenografts, confirming that our method faithfully reproduced human colon tumors. A drug sensitivity assay revealed that two of the primary cultures were hypersensitive to oxaliplatin rather than 5-FU, which was used in the patients, suggesting it as an effective therapeutic option. We thus present an effective, reproducible preclinical model for testing various personalized therapeutic options in colon cancer patients.
authors: Asan Institute for Life Science, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Hyang Sook
authors: HS
authors: Seol
authors: Hyo Jeong
authors: HJ
authors: Kang
authors: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Hyojeong
authors: H
authors: Kang
authors: Asan Institute for Life Science, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Seul-I
authors: SI
authors: Lee
authors: Asan Institute for Life Science, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Na Eun
authors: NE
authors: Kim
authors: Asan Institute for Life Science, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Tae Im
authors: TI
authors: Kim
authors: Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Sung Min
authors: SM
authors: Chun
authors: Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Tae Won
authors: TW
authors: Kim
authors: Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Chang Sik
authors: CS
authors: Yu
authors: Asan Institute for Life Science, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
authors: Young-Ah
authors: YA
authors: Suh
authors: Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA. Electronic address: singhshr@mail.nih.gov.
authors: Shree Ram
authors: SR
authors: Singh
authors: Asan Institute for Life Science, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea; Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. Electronic address: suhwan.chang@amc.seoul.kr.
authors: Suhwan
authors: S
authors: Chang
authors: Asan Institute for Life Science, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea; Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. Electronic address: jangsejin@amc.seoul.kr.
authors: Se Jin
authors: SJ
authors: Jang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009154:Mutation; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays / Q000379:methods*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: Colon cancer; Drug sensitivity; Oncomap analysis; Patient derived xenograft (PDX); Primary culture