title: Characterization of common marmoset dysgerminoma-like tumor induced by the lentiviral expression of reprogramming factors.
abstract: Recent generation of induced pluripotent stem (iPSCs) has made a significant impact on the field of human regenerative medicine. Prior to the clinical application of iPSCs, testing of their safety and usefulness must be carried out using reliable animal models of various diseases. In order to generate iPSCs from common marmoset (CM; Callithrix jacchus), one of the most useful experimental animals, we have lentivirally transduced reprogramming factors, including POU5F1 (also known as OCT3/4), SOX2, KLF4, and c-MYC into CM fibroblasts. The cells formed round colonies expressing embryonic stem cell markers, however, they showed an abnormal karyotype denoted as 46, X, del(4q), +mar, and formed human dysgerminoma-like tumors in SCID mice, indicating that the transduction of reprogramming factors caused unexpected tumorigenesis of CM cells. Moreover, CM dysgerminoma-like tumors were highly sensitive to DNA-damaging agents, irradiation, and fibroblast growth factor receptor inhibitor, and their growth was dependent on c-MYC expression. These results indicate that DNA-damaging agents, irradiation, fibroblast growth factor receptor inhibitor, and c-MYC-targeted therapies might represent effective treatment strategies for unexpected tumors in patients receiving iPSC-based therapy.
authors: Division of Molecular and Clinical Genetics, Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors: Saori
authors: S
authors: Yamaguchi
authors: Tomotoshi
authors: T
authors: Marumoto
authors: Takenobu
authors: T
authors: Nii
authors: Hirotaka
authors: H
authors: Kawano
authors: Jiyuan
authors: J
authors: Liao
authors: Yoko
authors: Y
authors: Nagai
authors: Michiyo
authors: M
authors: Okada
authors: Atsushi
authors: A
authors: Takahashi
authors: Hiroyuki
authors: H
authors: Inoue
authors: Erika
authors: E
authors: Sasaki
authors: Hiroshi
authors: H
authors: Fujii
authors: Shinji
authors: S
authors: Okano
authors: Hayao
authors: H
authors: Ebise
authors: Tetsuya
authors: T
authors: Sato
authors: Mikita
authors: M
authors: Suyama
authors: Hideyuki
authors: H
authors: Okano
authors: Yoshie
authors: Y
authors: Miura
authors: Kenzaburo
authors: K
authors: Tani
mesh_terms: D059786:Abnormal Karyotype; D000818:Animals; D002144:Callithrix; D063646:Carcinogenesis / Q000235:genetics*; D004407:Dysgerminoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D016086:Lentivirus; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C489427:MYC protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D016271:Proto-Oncogene Proteins c-myc; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
keywords: Common marmoset; FGFR; regenerating medicine; reprogramming factor; tumorigenesis