title: NUP160-SLC43A3 is a novel recurrent fusion oncogene in angiosarcoma.
abstract: Angiosarcoma is a malignant vascular tumor originating from endothelial cells of blood vessels or lymphatic vessels. The specific driver mutations in angiosarcoma remain unknown. In this study, we investigated this issue by transcriptome sequencing of patient-derived angiosarcoma cells (ISO-HAS), identifying a novel fusion gene NUP160-SLC43A3 found to be expressed in 9 of 25 human angiosarcoma specimens that were examined. In tumors harboring the fusion gene, the duration between the onset of symptoms and the first hospital visit was significantly shorter, suggesting more rapid tumor progression. Stable expression of the fusion gene in nontransformed human dermal microvascular endothelial cells elicited a gene-expression pattern mimicking ISO-HAS cells and increased cell proliferation, an effect traced in part to NUP160 truncation. Conversely, RNAi-mediated attenuation of NUP160 in ISO-HAS cells decreased cell number. Confirming the oncogenic effects of the fusion protein, subcutaneous implantation of NUP160-SLC43A3-expressing fibroblasts induced tumors resembling human angiosarcoma. Collectively, our findings advance knowledge concerning the genetic causes of angiosarcoma, with potential implications for new diagnostic and therapeutic approaches.
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Shimozono
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. mjin@kumamoto-u.ac.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Jinnin
authors.affiliation: Department of Dermatology, Kitasato University School of Medicine, Kitasato, Kanagawa, Japan.
authors.forename: Mamiko
authors.initials: M
authors.lastname: Masuzawa
authors.affiliation: Department of Molecular Diagnostics, School of Allied Health Sciences, Kitasato University, Kitasato, Kanagawa, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Masuzawa
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Zhongzhi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Hirano
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Tomizawa
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Etoh-Kira
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Ikko
authors.initials: I
authors.lastname: Kajihara
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Harada
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukushima
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ihn
mesh_terms: D016475:3T3 Cells; D026905:Amino Acid Transport Systems; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D006394:Hemangiosarcoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D042601:Lymphatic Vessels / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D028861:Nuclear Pore Complex Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D017422:Sequence Analysis, DNA; D059467:Transcriptome / Q000235:genetics; D014183:Transplantation, Heterologous
chemical_list: D026905:Amino Acid Transport Systems; C440251:NUP160 protein, human; C000605141:NUP160-SLC43A3 fusion protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C000605140:SLC43A3 protein, human