2010年8月5日木曜日

癌と突然変異について:Natureの最新論文

Natureのオンラインで乳癌、肺癌、卵巣癌、前立腺癌の変異遺伝子リスト論文が出た。論文提出から一年以上経つが、よくnatureの査読に耐えたものだね・・・・というようなことが話題になる論文。Laura D Woodの論文以来、この類いの論文は実はそうたくさん出ている訳でない。いくつかたまると教科書が書き換えられることになる。

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2007年11月29日木曜日

Laura D.Woodの大腸癌遺伝子解析
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Letter

Nature advance online publication 28 July 2010 |Received 23 July 2009; Accepted 27 May 2010; Published online 28 July 2010

Diverse somatic mutation patterns and pathway alterations in human cancers

Zhengyan Kan1,2, Bijay S. Jaiswal1, Jeremy Stinson1, Vasantharajan Janakiraman1, Deepali Bhatt1, Howard M. Stern3, Peng Yue2, Peter M. Haverty2, Richard Bourgon2, Jianbiao Zheng4, Martin Moorhead4, Subhra Chaudhuri1, Lynn P. Tomsho5, Brock A. Peters1, Kanan Pujara1, Shaun Cordes1, David P. Davis1, Victoria E. H. Carlton4, Wenlin Yuan1, Li Li2, Weiru Wang6, Charles Eigenbrot6, Joshua S. Kaminker2, David A. Eberhard3, Paul Waring3, Stephan C. Schuster5, Zora Modrusan1, Zemin Zhang2, David Stokoe1, Frederic J. de Sauvage1, Malek Faham4 & Somasekar Seshagiri1

  1. Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
  2. Department of Bioinformatics, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
  3. Department of Pathology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
  4. Affymetrix Inc, 3420 Central Expressway, Santa Clara, California 95051, USA
  5. Pennsylvania State University, Center for Comparative Genomics and Bioinformatics, 310 Wartik Lab, University Park, Pennsylvania 16802, USA
  6. Department of Protein Engineering, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA

Correspondence to: Somasekar Seshagiri1 Email: sekar@gene.com

The systematic characterization of somatic mutations in cancer genomes is essential for understanding the disease and for developing targeted therapeutics1. Here we report the identification of 2,576 somatic mutations across ~1,800megabases of DNA representing 1,507 coding genes from 441 tumours comprising breast, lung, ovarian and prostate cancer types and subtypes. We found that mutation rates and the sets of mutated genes varied substantially across tumour types and subtypes. Statistical analysis identified 77 significantly mutated genes including protein kinases, G-protein-coupled receptors such as GRM8, BAI3, AGTRL1 (also called APLNR) and LPHN3, and other druggable targets. Integrated analysis of somatic mutations and copy number alterations identified another 35 significantly altered genes including GNAS, indicating an expanded role for Gα subunits in multiple cancer types. Furthermore, our experimental analyses demonstrate the functional roles of mutant GNAO1 (a Gα subunit) and mutant MAP2K4 (a member of the JNK signalling pathway) in oncogenesis. Our study provides an overview of the mutational spectra across major human cancers and identifies several potential therapeutic targets.

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