Characterizing the cancer genome in lung adenocarcinoma

Nature 450, 893-898 (06 December 2007) . Published: 2007.12.05

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 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 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

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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 tumors (n=371) using dense single nucleotide polymorphism (SNP) arrays, we identify a total of 57 significantly recurrent events. We find that 26 of 39 autosomal chromosome arms show consistent 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 6 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. Based on genomic and functional analysis, we identify NKX2-1 (TITF1), which lies in the 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 play a role in lung adenocarcinoma remain to be discovered.

Keywords: Lung SNP array adenocarcinoma copy number

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Supplemental Data

Description Link/Filename
Paper text Weir_Nature2007.doc
Website - (datasets and supplemental info)
Figure 1 fig1.pdf
Processed raw copy number datafile viewable in GenePattern
Figure 2 fig2.pdf
Raw .CEL files - Tumors#1
Figure 3 fig3.pdf
Raw .CEL files - Tumors#2
Raw .CEL files - Tumors#3
Full supplementary information Weir_supplement.pdf
Raw .CEL files - Normals#1
Sample information file - TSP samples Newsampleinfo_TSP.xls
Sample information file - non-TSP samples sampleinfo_non-TSP.xls
Raw .CEL files - Normals#2
Viewable file of GISTIC scores for high threshold TSP_highthresh_scores.txt
Raw .CEL files - Normals#3
Viewable file of GISIC scores for low threshold TSP_lowthresh_scores.txt
Website for Tumor Sequencing Project (TSP)
Processed smoothed copy number datafile viewable in GenePattern