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タイトル: | Systematic analysis of mutation distribution in three dimensional protein structures identifies cancer driver genes. |
著者: | Fujimoto, Akihiro ![]() Okada, Yukinori Boroevich, Keith A Tsunoda, Tatsuhiko Taniguchi, Hiroaki Nakagawa, Hidewaki |
著者名の別形: | 藤本, 明洋 |
発行日: | 26-May-2016 |
出版者: | Nature Publishing Group |
誌名: | Scientific reports |
巻: | 6 |
論文番号: | 26483 |
抄録: | Protein tertiary structure determines molecular function, interaction, and stability of the protein, therefore distribution of mutation in the tertiary structure can facilitate the identification of new driver genes in cancer. To analyze mutation distribution in protein tertiary structures, we applied a novel three dimensional permutation test to the mutation positions. We analyzed somatic mutation datasets of 21 types of cancers obtained from exome sequencing conducted by the TCGA project. Of the 3, 622 genes that had ≥3 mutations in the regions with tertiary structure data, 106 genes showed significant skew in mutation distribution. Known tumor suppressors and oncogenes were significantly enriched in these identified cancer gene sets. Physical distances between mutations in known oncogenes were significantly smaller than those of tumor suppressors. Twenty-three genes were detected in multiple cancers. Candidate genes with significant skew of the 3D mutation distribution included kinases (MAPK1, EPHA5, ERBB3, and ERBB4), an apoptosis related gene (APP), an RNA splicing factor (SF1), a miRNA processing factor (DICER1), an E3 ubiquitin ligase (CUL1) and transcription factors (KLF5 and EEF1B2). Our study suggests that systematic analysis of mutation distribution in the tertiary protein structure can help identify cancer driver genes. |
記述: | タンパク質の立体構造上の変異解析により治療標的となり得るがん遺伝子を検出. 京都大学プレスリリース. 2016-06-01. |
著作権等: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
URI: | http://hdl.handle.net/2433/214349 |
DOI(出版社版): | 10.1038/srep26483 |
PubMed ID: | 27225414 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2016-06-01 |
出現コレクション: | 学術雑誌掲載論文等 |
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