ムラガキ　ヨシヒロ   Muragaki Yoshihiro   村垣　善浩    所属   医学部 医学科（東京女子医科大学病院）    職種   客員教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Mutational landscape and clonal architecture in grade II and III gliomas
掲載誌名	正式名：Nature genetics 略　 称：Nat Genet ISSNコード：15461718 (Electronic)10614036 (Linking)
掲載区分	国外
巻・号・頁	47(5),pp.458-68-468
著者・共著者	SUZUKI Hiromichi†, AOKI Kosuke, CHIBA Kenichi, SATO Yusuke, SHIOZAWA Yusuke, SHIRAISHI Yuichi, SHIMAMURA Teppei, NIIDA Atsushi, MOTOMURA Kazuya, OHKA Fumiharu, YAMAMOTO Takashi, TANAHASHI Kuniaki, RANJIT Melissa, WAKABAYASHI Toshihiko, YOSHIZATO Tetsuichi, KATAOKA Keisuke, YOSHIDA Kenichi, NAGATA Yasunobu, SATO-OTSUBO Aiko, TANAKA Hiroko, SANADA Masashi, KONDO Yutaka, NAKAMURA Hideo, MIZOGUCHI Masahiro, ABE Tatsuya, MURAGAKI Yoshihiro, WATANABE Reiko, ITO Ichiro, NIYANO Satoru, NATSUME Atsushi, OGAWA Seishi
発行年月	2015/05
概要	Grade II and III gliomas are generally slowly progressing brain cancers, many of which eventually transform into more aggressive tumors. Despite recent findings of frequent mutations in IDH1 and other genes, knowledge about their pathogenesis is still incomplete. Here, combining two large sets of high-throughput sequencing data, we delineate the entire picture of genetic alterations and affected pathways in these glioma types, with sensitive detection of driver genes. Grade II and III gliomas comprise three distinct subtypes characterized by discrete sets of mutations and distinct clinical behaviors. Mutations showed significant positive and negative correlations and a chronological hierarchy, as inferred from different allelic burdens among coexisting mutations, suggesting that there is functional interplay between the mutations that drive clonal selection. Extensive serial and multi-regional sampling analyses further supported this finding and also identified a high degree of temporal and spatial heterogeneity generated during tumor expansion and relapse, which is likely shaped by the complex but ordered processes of multiple clonal selection and evolutionary events.
DOI	10.1038/ng.3273
文献番号	25848751