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 Kan^1,2, 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

Abstract

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 ~1,800 megabases 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.