美国哈佛大学和麻省理工学院的科学家在对与肺癌有关的基因变异进行“拼图”后，发现一种在肺癌细胞扩散中发挥关键作用的基因。
这项最新研究报告４日登于英国《自然》杂志网站上。报告说，两所高校合办的布罗德研究所研究人员已经测定一种名为ＮＫＸ２.１的重要基因，这种基因能够促进癌细胞生长。
大部分人类癌症缘自ＤＮＡ（脱氧核糖核酸）变异，这些变异贯穿于人的一生，不断在细胞中积累。但是，这些变异的性质和后果究竟如何，尚不清楚。
研究人员在５００多个肿瘤样本中寻找ＤＮＡ变异。这些肿瘤样本都采集于肺癌病人。
研究人员将重点放在肺腺癌上。这种癌症占所有肺癌病例近三分之一。
他们使用一种“刀刃”技术，扫描这些基因，从中寻找单核苷酸多态性（即基因遗传密码突变）。单核苷酸多态性凸显出基因编码片断发生消失或复制。
研究人员共发现５７种常见于癌症病人的基因变异，其中至少４０种变异与涉及肺腺癌的基因有关，而科学家此前并不知道这些变异的基因与肺腺癌有关。
出现频率最高的基因变异发生在ＮＫＸ２.１基因上。研究人员将这种基因称为癌细胞生长的催化剂。
科学家此前只是知道，ＮＫＸ２.１通常作为“主调节器”控制肺泡细胞中其他基因的活动。
“这是对癌症基因组的新视角，无论在广度还是深度上都前所未有，”领导这项研究的马修·梅耶松说，“它打下了重要基础。”
研究人员说，这一发现有望帮助科学家研制克服癌症的新药，不仅针对肺癌，还可以针对其他癌症。他们采用的研究技术也将有助于分析其他癌症。
世界卫生组织发布的数据显示，肺癌每年导致全世界约１３０万人死亡，已成为死亡率最高的癌症。（新华社）
原始出处:
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: matthew_meyerson@dfci.harvard.edu).
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.
