Cancer Program Publication

Characterizing the cancer genome in lung adenocarcinoma
ProjectSNP Analysis
Additional Projects/
Categories		 Lung Cancer
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 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.
AuthorsBarbara 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
Publication Date12/06/2007
Contact emails matthew_meyerson@dfci.harvard.edu
Publication URLhttp://www.nature.com/nature/journal/v450/n7171/abs/nature06358.html
CitationNature 450, 893-898 (06 December 2007)
KeywordsSNP array; Lung; adenocarcinoma; copy number
 
Supplemental Information
URLs
NameURL
Website - (datasets and supplemental info)http://www.broad.mit.edu/cancer/pub/tsp
Processed raw copy number datafile viewable in GenePatternftp://ftp.broad.mit.edu/outgoing/TSP/371_raw.cn
Raw .CEL files - Tumors#1ftp://ftp.broad.mit.edu/outgoing/TSP/tumors1.zip
Raw .CEL files - Tumors#2ftp://ftp.broad.mit.edu/outgoing/TSP/tumors2.zip
Raw .CEL files - Tumors#3ftp://ftp.broad.mit.edu/outgoing/TSP/tumors3.zip
Raw .CEL files - Normals#1ftp://ftp.broad.mit.edu/outgoing/TSP/normals1.zip
Raw .CEL files - Normals#2ftp://ftp.broad.mit.edu/outgoing/TSP/normals2.zip
Raw .CEL files - Normals#3ftp://ftp.broad.mit.edu/outgoing/TSP/normals3.zip
Website for Tumor Sequencing Project (TSP)http://caintegrator-info.nci.nih.gov/csp
Processed smoothed copy number datafile viewable in GenePatternftp://ftp.broad.mit.edu/outgoing/TSP/371_smoothed.snp
Files
DescriptionFile
Paper textWeir_Nature2007.doc
Figure 1fig1.pdf
Figure 2fig2.pdf
Figure 3fig3.pdf
Full supplementary informationWeir_supplement.pdf
Sample information file - TSP samplesNewsampleinfo_TSP.xls
Sample information file - non-TSP samplessampleinfo_non-TSP.xls
Viewable file of GISTIC scores for high thresholdTSP_highthresh_scores.txt
Viewable file of GISIC scores for low thresholdTSP_lowthresh_scores.txt