美國哈佛大學和麻省理工學院的科學家在對與肺癌有關的基因變異進行“拼圖”后，發(fā)現(xiàn)一種在肺癌細胞擴散中發(fā)揮關鍵作用的基因,。
這項最新研究報告４日登于英國《自然》雜志網(wǎng)站上,。報告說，兩所高校合辦的布羅德研究所研究人員已經(jīng)測定一種名為ＮＫＸ２.１的重要基因,，這種基因能夠促進癌細胞生長,。
大部分人類癌癥緣自ＤＮＡ（脫氧核糖核酸）變異，這些變異貫穿于人的一生，不斷在細胞中積累,。但是,，這些變異的性質和后果究竟如何，尚不清楚,。
研究人員在５００多個腫瘤樣本中尋找ＤＮＡ變異,。這些腫瘤樣本都采集于肺癌病人。
研究人員將重點放在肺腺癌上,。這種癌癥占所有肺癌病例近三分之一,。
他們使用一種“刀刃”技術，掃描這些基因,，從中尋找單核苷酸多態(tài)性（即基因遺傳密碼突變）,。單核苷酸多態(tài)性凸顯出基因編碼片斷發(fā)生消失或復制。
研究人員共發(fā)現(xiàn)５７種常見于癌癥病人的基因變異,，其中至少４０種變異與涉及肺腺癌的基因有關,，而科學家此前并不知道這些變異的基因與肺腺癌有關。
出現(xiàn)頻率最高的基因變異發(fā)生在ＮＫＸ２.１基因上,。研究人員將這種基因稱為癌細胞生長的催化劑,。
科學家此前只是知道，ＮＫＸ２.１通常作為“主調節(jié)器”控制肺泡細胞中其他基因的活動,。
“這是對癌癥基因組的新視角,，無論在廣度還是深度上都前所未有，”領導這項研究的馬修·梅耶松說,，“它打下了重要基礎,。”
研究人員說，這一發(fā)現(xiàn)有望幫助科學家研制克服癌癥的新藥,，不僅針對肺癌,，還可以針對其他癌癥。他們采用的研究技術也將有助于分析其他癌癥,。
世界衛(wèi)生組織發(fā)布的數(shù)據(jù)顯示,，肺癌每年導致全世界約１３０萬人死亡，已成為死亡率最高的癌癥,。（新華社）
原始出處:
Nature advance online publication 4 November 2007 | doi:10.1038/nature06358; Received 12 April 2007; Accepted 10 October 2007; Published online 4 November 2007
Characterizing the cancer genome in lung adenocarcinoma
Barbara A. Weir1,2,27, Michele S. Woo1,27, Gad Getz2,27, Sven Perner3,4, Li Ding5, Rameen Beroukhim1,2, William M. Lin1,2, Michael A. Province6, Aldi Kraja6, Laura A. Johnson3, Kinjal Shah1,2, Mitsuo Sato8, Roman K. Thomas1,2,9,10, Justine A. Barletta3, Ingrid B. Borecki6, Stephen Broderick11,12, Andrew C. Chang14, Derek Y. Chiang1,2, Lucian R. Chirieac3,16, Jeonghee Cho1, Yoshitaka Fujii18, Adi F. Gazdar8, Thomas Giordano15, Heidi Greulich1,2, Megan Hanna1,2, Bruce E. Johnson1, Mark G. Kris11, Alex Lash11, Ling Lin5, Neal Lindeman3,16, Elaine R. Mardis5, John D. McPherson19, John D. Minna8, Margaret B. Morgan19, Mark Nadel1,2, Mark B. Orringer14, John R. Osborne5, Brad Ozenberger20, Alex H. Ramos1,2, James Robinson2, Jack A. Roth21, Valerie Rusch11, Hidefumi Sasaki18, Frances Shepherd25, Carrie Sougnez2, Margaret R. Spitz22, Ming-Sound Tsao25, David Twomey2, Roel G. W. Verhaak2, George M. Weinstock19, David A. Wheeler19, Wendy Winckler1,2, Akihiko Yoshizawa11, Soyoung Yu1, Maureen F. Zakowski11, Qunyuan Zhang6, David G. Beer14, Ignacio I. Wistuba23,24, Mark A. Watson7, Levi A. Garraway1,2, Marc Ladanyi11,12, William D. Travis11, William Pao11,12, Mark A. Rubin2,3, Stacey B. Gabriel2, Richard A. Gibbs19, Harold E. Varmus13, Richard K. Wilson5, Eric S. Lander2,17,26 & Matthew Meyerson1,2,16
Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
Cancer Program, Genetic Analysis Platform, and Genome Biology Program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
Institute of Pathology, University of Ulm, Ulm 89081, Germany
Genome Sequencing Center,
Division of Statistical Genomics and,
Department of Pathology and Immunology, Washington University in Saint Louis, Saint Louis, Missouri 63130, USA
University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max-Planck Society and the Medical Faculty of the University of Cologne, Cologne 50931, Germany
Center for Integrated Oncology and Department I for Internal Medicine, University of Cologne, Cologne 50931, Germany
Departments of Medicine, Surgery, Pathology, and Computational Biology,
Human Oncology and Pathogenesis Program,
Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA
Section of Thoracic Surgery, Department of Surgery and,
Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA
Department of Pathology and,
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
Department of Surgery, Nagoya City University Medical School, Nagoya 467-8602, Japan
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Department of Thoracic and Cardiovascular Surgery,
Department of Epidemiology,
Department of Pathology and,
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA
University Health Network and Princess Margaret Hospital, Toronto M5G 2C4, Canada
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
These authors contributed equally to this work.
Correspondence to: Matthew Meyerson1,2,16 Correspondence and requests for materials should be addressed to M.M. (Email: [email protected]).
Somatic alterations in cellular DNA underlie almost all human cancers1. The prospect of targeted therapies2 and the development of high-resolution, genome-wide approaches3, 4, 5, 6, 7, 8 are now spurring systematic efforts to characterize cancer genomes. Here we report a large-scale project to characterize copy-number alterations in primary lung adenocarcinomas. By analysis of a large collection of tumours (n = 371) using dense single nucleotide polymorphism arrays, we identify a total of 57 significantly recurrent events. We find that 26 of 39 autosomal chromosome arms show consistent large-scale copy-number gain or loss, of which only a handful have been linked to a specific gene. We also identify 31 recurrent focal events, including 24 amplifications and 7 homozygous deletions. Only six of these focal events are currently associated with known mutations in lung carcinomas. The most common event, amplification of chromosome 14q13.3, is found in 12% of samples. On the basis of genomic and functional analyses, we identify NKX2-1 (NK2 homeobox 1, also called TITF1), which lies in the minimal 14q13.3 amplification interval and encodes a lineage-specific transcription factor, as a novel candidate proto-oncogene involved in a significant fraction of lung adenocarcinomas. More generally, our results indicate that many of the genes that are involved in lung adenocarcinoma remain to be discovered.
