ムラガキ ヨシヒロ   MURAGAKI Yoshihiro
  村垣 善浩
   所属   研究施設 研究施設
   職種   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),458-68-468頁
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