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J-GLOBAL ID：201802229146117040   整理番号：18A1684458

遺伝性骨髄不全症候群における生殖系列TP53を活性化するde novo変異【JST・京大機械翻訳】

De Novo Mutations Activating Germline TP53 in an Inherited Bone-Marrow-Failure Syndrome

著者 (50件)： Toki Tsutomu (Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan) ,  Yoshida Kenichi (Cancer Genomics Project, Graduate School of Medicine, the University of Tokyo, Tokyo 113-00333, Japan) ,  Yoshida Kenichi (Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan) ,  Wang RuNan (Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan) ,  Wang RuNan (Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China) ,  Nakamura Sou (Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan) ,  Maekawa Takanobu (Department of General Pediatric and Interdisciplinary Medicine, National Center for Child Health and Development, Tokyo 157-8535, Japan) ,  Goi Kumiko (Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan) ,  Katoh Megumi C. (Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan) ,  Katoh Megumi C. (Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba 305-8575, Japan) ,  Mizuno Seiya (Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba 305-8575, Japan) ,  Sugiyama Fumihiro (Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba 305-8575, Japan) ,  Kanezaki Rika (Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan) ,  Uechi Tamayo (Frontier Science Research Center, University of Miyazaki, Miyazaki 889-1692, Japan) ,  Nakajima Yukari (Frontier Science Research Center, University of Miyazaki, Miyazaki 889-1692, Japan) ,  Sato Yusuke (Cancer Genomics Project, Graduate School of Medicine, the University of Tokyo, Tokyo 113-00333, Japan) ,  Sato Yusuke (Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan) ,  Okuno Yusuke (Cancer Genomics Project, Graduate School of Medicine, the University of Tokyo, Tokyo 113-00333, Japan) ,  Okuno Yusuke (Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan) ,  Sato-Otsubo Aiko (Cancer Genomics Project, Graduate School of Medicine, the University of Tokyo, Tokyo 113-00333, Japan) ,  Sato-Otsubo Aiko (Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan) ,  Shiozawa Yusuke (Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan) ,  Kataoka Keisuke (Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan) ,  Shiraishi Yuichi (Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, the University of Tokyo, Tokyo 108-8639, Japan) ,  Sanada Masashi (Cancer Genomics Project, Graduate School of Medicine, the University of Tokyo, Tokyo 113-00333, Japan) ,  Sanada Masashi (Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan) ,  Chiba Kenichi (Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, the University of Tokyo, Tokyo 108-8639, Japan) ,  Tanaka Hiroko (Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, the University of Tokyo, Tokyo 108-8639, Japan) ,  Terui Kiminori (Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan) ,  Sato Tomohiko (Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan) ,  Kamio Takuya (Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan) ,  Sakaguchi Hirotoshi (Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan) ,  Ohga Shouichi (Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan) ,  Kuramitsu Madoka (Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo 208-0011, Japan) ,  Hamaguchi Isao (Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo 208-0011, Japan) ,  Ohara Akira (Department of Pediatrics, Omori Medical Center, Toho University, Tokyo 143-8540, Japan) ,  Kanno Hitoshi (Department of Transfusion Medicine and Cell Processing, Tokyo Women’s Medical University, Tokyo 162-8666, Japan) ,  Miyano Satoru (Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, the University of Tokyo, Tokyo 108-8639, Japan) ,  Miyano Satoru (Laboratory of Sequence Analysis, Human Genome Center, Institute of Medical Science, the University of Tokyo, Tokyo 108-8639, Japan) ,  Kojima Seiji (Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan) ,  Ishiguro Akira (Division of Hematology, National Center for Child Health and Development, Tokyo 157-8535, Japan) ,  Sugita Kanji (Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan) ,  Kenmochi Naoya (Frontier Science Research Center, University of Miyazaki, Miyazaki 889-1692, Japan) ,  Takahashi Satoru (Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan) ,  Takahashi Satoru (Laboratory Animal Resource Center, Faculty of Medicine, University of Tsukuba 305-8575, Japan) ,  Eto Koji (Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan) ,  Ogawa Seishi (Cancer Genomics Project, Graduate School of Medicine, the University of Tokyo, Tokyo 113-00333, Japan) ,  Ogawa Seishi (Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan) ,  Ogawa Seishi (Department of Medicine, Karolinska Institute, Center for Hematology and Regenerative Medicine, SE-171 76 Stockholm, Sweden) ,  Ito Etsuro (Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan)
資料名： American Journal of Human Genetics  (American Journal of Human Genetics)
巻： 103  号： 3  ページ： 440-447  発行年： 2018年 
JST資料番号： B0360B  ISSN： 0002-9297  資料種別： 逐次刊行物 (A)
記事区分： 短報  発行国： オランダ (NLD)  言語： 英語 (EN)

抄録/ポイント： 遺伝性骨髄不全症候群(IBMFS)は,骨髄不全,先天異常および悪性腫瘍のリスク増加により特徴付けられる不均一な遺伝的疾患を含む。多くの証拠は,p53の活性化が,Diamond-Blackfan貧血(DBA)およびdysskeratosis congita(DC)を含むIBMFSの病因に中心的である可能性があることを示唆している。しかしながら,各臨床的特徴におけるp53活性化の正確な役割は不明のままである。ここでは,低ガンマグロブリン血症,成長遅延および微小脳模倣DBAおよびDCを伴うIBMFSを有する2人の個人で見出されたユニークなde novo TP53生殖系列変異体を報告する。TP53はヒト癌において最も頻繁に変異する腫瘍抑制遺伝子であり,Li-Fraumini癌素因症候群においてしばしば生殖系列変異体が発生する。これらの突然変異の大部分はコアDNA結合ドメインに影響し,転写活性の低下をもたらす。対照的に,ここで研究した2つの個体で見出された変異体は,蛋白質の同じ切断を引き起こし,C末端ドメイン(CTD)から32残基の損失をもたらした。予想外に,p53変異体は転写活性を増強し,以前にヒトでは記述されていなかった。ゼブラフィッシュおよびヒト誘導多能性幹細胞においてこの変異体を発現させると,赤血球産生の障害が観察された。これらの知見は,CTDを欠くTP53の公表されたknock インマウスモデルとの密接な類似性と共に,TP53のCTD切断変異がIBMFSを引き起こし,p53とIBMFSの間の以前に仮定された結合に重要な洞察を提供することを示す。Copyright 2018 Elsevier B.V., Amsterdam. All rights reserved. Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： 突然変異 ,  皮膚病 ,  p53タンパク質 ,  ゼブラフィッシュ ,  ヒト ,  *遺伝 ,  癌抑制遺伝子 ,  病因 ,  貧血 ,  多能性幹細胞 ,  *TP53 ,  *生殖系列 ,  *遺伝的変異
準シソーラス用語： *変異 ,  悪性腫瘍 ,  *骨髄機能不全 , 【Automatic Indexing@JST】

著者キーワード (10件)： TP53 ,  p53 ,  C末端ドメイン ,  遺伝性骨髄不全症候群 ,  ダイヤモンド-ブラックファン貧血 ,  先天性皮膚疾患 ,  ゼブラフィッシュ ,  ヒト誘導多能性幹細胞 ,  IPSC ,  遺伝子編集

分類 (3件)： 血液の腫よう  (GK04000M) ,  腫ようの診断  (GE03020J) ,  血液の疾患  (GK03000F)

タイトルに関連する用語 (5件)： 遺伝性骨髄不全症候群 ,  生殖系列 ,  TP53 ,  活性化 ,  変異