Characterizing the cancer genome in lung adenocarcinoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-12

AUTHORS

Barbara A. Weir, Michele S. Woo, Gad Getz, Sven Perner, Li Ding, Rameen Beroukhim, William M. Lin, Michael A. Province, Aldi Kraja, Laura A. Johnson, Kinjal Shah, Mitsuo Sato, Roman K. Thomas, Justine A. Barletta, Ingrid B. Borecki, Stephen Broderick, Andrew C. Chang, Derek Y. Chiang, Lucian R. Chirieac, Jeonghee Cho, Yoshitaka Fujii, Adi F. Gazdar, Thomas Giordano, Heidi Greulich, Megan Hanna, Bruce E. Johnson, Mark G. Kris, Alex Lash, Ling Lin, Neal Lindeman, Elaine R. Mardis, John D. McPherson, John D. Minna, Margaret B. Morgan, Mark Nadel, Mark B. Orringer, John R. Osborne, Brad Ozenberger, Alex H. Ramos, James Robinson, Jack A. Roth, Valerie Rusch, Hidefumi Sasaki, Frances Shepherd, Carrie Sougnez, Margaret R. Spitz, Ming-Sound Tsao, David Twomey, Roel G. W. Verhaak, George M. Weinstock, David A. Wheeler, Wendy Winckler, Akihiko Yoshizawa, Soyoung Yu, Maureen F. Zakowski, Qunyuan Zhang, David G. Beer, Ignacio I. Wistuba, Mark A. Watson, Levi A. Garraway, Marc Ladanyi, William D. Travis, William Pao, Mark A. Rubin, Stacey B. Gabriel, Richard A. Gibbs, Harold E. Varmus, Richard K. Wilson, Eric S. Lander, Matthew Meyerson

ABSTRACT

Somatic alterations in cellular DNA underlie almost all human cancers. The prospect of targeted therapies and the development of high-resolution, genome-wide approaches 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 approximately 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. More... »

PAGES

893

Journal

TITLE

Nature

ISSUE

7171

VOLUME

450

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature06358

DOI

http://dx.doi.org/10.1038/nature06358

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1019681472

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17982442


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823 https://www.grid.ac/institutes/grid.6190.e schema:alternateName University of Cologne
824 schema:name Cancer Program, Genetic Analysis Platform, and Genome Biology Program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA
825 Center for Integrated Oncology and Department I for Internal Medicine, University of Cologne, Cologne 50931, Germany
826 Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
827 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
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830 schema:name Cancer Program, Genetic Analysis Platform, and Genome Biology Program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA
831 Department of Pathology and,
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835 schema:name Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
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837 https://www.grid.ac/institutes/grid.6582.9 schema:alternateName University of Ulm
838 schema:name Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts 02115, USA
839 Institute of Pathology, University of Ulm, Ulm 89081, Germany
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841 https://www.grid.ac/institutes/grid.66859.34 schema:alternateName Broad Institute
842 schema:name Cancer Program, Genetic Analysis Platform, and Genome Biology Program, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA
843 Department of Medical Oncology and Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
844 Department of Pathology and,
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