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- Title
Characterizing the cancer genome in lung adenocarcinoma.
- Authors
Weir, Barbara A; Woo, Michele S; Getz, Gad; Perner, Sven; Ding, Li; Beroukhim, Rameen; Lin, William M; Province, Michael A; Kraja, Aldi; Johnson, Laura A; Shah, Kinjal; Sato, Mitsuo; Thomas, Roman K; Barletta, Justine A; Borecki, Ingrid B; Broderick, Stephen; Chang, Andrew C; Chiang, Derek Y; Chirieac, Lucian R; Cho, Jeonghee; Fujii, Yoshitaka; Gazdar, Adi F; Giordano, Thomas; Greulich, Heidi; Hanna, Megan; Johnson, Bruce E; Kris, Mark G; Lash, Alex; Lin, Ling; Lindeman, Neal; Mardis, Elaine R; McPherson, John D; Minna, John D; Morgan, Margaret B; Nadel, Mark; Orringer, Mark B; Osborne, John R; Ozenberger, Brad; Ramos, Alex H; Robinson, James; Roth, Jack A; Rusch, Valerie; Sasaki, Hidefumi; Shepherd, Frances; Sougnez, Carrie; Spitz, Margaret R; Tsao, Ming-Sound; Twomey, David; Verhaak, Roel G W; Weinstock, George M; Wheeler, David A; Winckler, Wendy; Yoshizawa, Akihiko; Yu, Soyoung; Zakowski, Maureen F; Zhang, Qunyuan; Beer, David G; Wistuba, Ignacio I; Watson, Mark A; Garraway, Levi A; Ladanyi, Marc; Travis, William D; Pao, William; Rubin, Mark A; Gabriel, Stacey B; Gibbs, Richard A; Varmus, Harold E; Wilson, Richard K; Lander, Eric S; Meyerson, Matthew
- 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.
- Publication
Nature, 2007, Vol 450, Issue 7171, p893
- ISSN
1476-4687
- Publication type
Journal Article
- DOI
10.1038/nature06358