%0 Journal Article %1 suzuki2015mutational %A Suzuki, Hiromichi %A Aoki, Kosuke %A Chiba, Kenichi %A Sato, Yusuke %A Shiozawa, Yusuke %A Shiraishi, Yuichi %A Shimamura, Teppei %A Niida, Atsushi %A Motomura, Kazuya %A Ohka, Fumiharu %A Yamamoto, Takashi %A Tanahashi, Kuniaki %A Ranjit, Melissa %A Wakabayashi, Toshihiko %A Yoshizato, Tetsuichi %A Kataoka, Keisuke %A Yoshida, Kenichi %A Nagata, Yasunobu %A Sato-Otsubo, Aiko %A Tanaka, Hiroko %A Sanada, Masashi %A Kondo, Yutaka %A Nakamura, Hideo %A Mizoguchi, Masahiro %A Abe, Tatsuya %A Muragaki, Yoshihiro %A Watanabe, Reiko %A Ito, Ichiro %A Miyano, Satoru %A Natsume, Atsushi %A Ogawa, Seishi %D 2015 %I Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. %J Nat Genet %K %N 5 %P 458--468 %T Mutational landscape and clonal architecture in grade II and III gliomas %U http://dx.doi.org/10.1038/ng.3273 %V 47 %X 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.

@article{suzuki2015mutational, abstract = {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.}, added-at = {2019-02-24T11:44:30.000+0100}, author = {Suzuki, Hiromichi and Aoki, Kosuke and Chiba, Kenichi and Sato, Yusuke and Shiozawa, Yusuke and Shiraishi, Yuichi and Shimamura, Teppei and Niida, Atsushi and Motomura, Kazuya and Ohka, Fumiharu and Yamamoto, Takashi and Tanahashi, Kuniaki and Ranjit, Melissa and Wakabayashi, Toshihiko and Yoshizato, Tetsuichi and Kataoka, Keisuke and Yoshida, Kenichi and Nagata, Yasunobu and Sato-Otsubo, Aiko and Tanaka, Hiroko and Sanada, Masashi and Kondo, Yutaka and Nakamura, Hideo and Mizoguchi, Masahiro and Abe, Tatsuya and Muragaki, Yoshihiro and Watanabe, Reiko and Ito, Ichiro and Miyano, Satoru and Natsume, Atsushi and Ogawa, Seishi}, biburl = {https://www.bibsonomy.org/bibtex/2bb7e8f41fb29888a772f6fabaaf9febd/marcsaric}, interhash = {124418ad6a9176ccbfc0577bb804070f}, intrahash = {bb7e8f41fb29888a772f6fabaaf9febd}, issn = {10614036}, journal = {Nat Genet}, keywords = {}, month = may, number = 5, pages = {458--468}, publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.}, timestamp = {2019-02-24T11:44:30.000+0100}, title = {Mutational landscape and clonal architecture in grade II and III gliomas}, url = {http://dx.doi.org/10.1038/ng.3273}, volume = 47, year = 2015 }