%0 Journal Article %J Nature %D 2007 %T Characterizing the cancer genome in lung adenocarcinoma. %A Weir, Barbara A %A Woo, Michele S %A Getz, Gad %A Perner, Sven %A Ding, Li %A Beroukhim, Rameen %A Lin, William M %A Province, Michael A %A Kraja, Aldi %A Johnson, Laura A %A Shah, Kinjal %A Sato, Mitsuo %A Thomas, Roman K %A Barletta, Justine A %A Borecki, Ingrid B %A Broderick, Stephen %A Chang, Andrew C %A Chiang, Derek Y %A Chirieac, Lucian R %A Cho, Jeonghee %A Fujii, Yoshitaka %A Gazdar, Adi F %A Giordano, Thomas %A Greulich, Heidi %A Hanna, Megan %A Johnson, Bruce E %A Kris, Mark G %A Lash, Alex %A Lin, Ling %A Lindeman, Neal %A Mardis, Elaine R %A McPherson, John D %A Minna, John D %A Morgan, Margaret B %A Nadel, Mark %A Orringer, Mark B %A Osborne, John R %A Ozenberger, Brad %A Ramos, Alex H %A Robinson, James %A Roth, Jack A %A Rusch, Valerie %A Sasaki, Hidefumi %A Shepherd, Frances %A Sougnez, Carrie %A Spitz, Margaret R %A Tsao, Ming-Sound %A Twomey, David %A Verhaak, Roel G W %A Weinstock, George M %A Wheeler, David A %A Winckler, Wendy %A Yoshizawa, Akihiko %A Yu, Soyoung %A Zakowski, Maureen F %A Zhang, Qunyuan %A Beer, David G %A Wistuba, Ignacio I %A Watson, Mark A %A Garraway, Levi A %A Ladanyi, Marc %A Travis, William D %A Pao, William %A Rubin, Mark A %A Gabriel, Stacey B %A Gibbs, Richard A %A Varmus, Harold E %A Wilson, Richard K %A Lander, Eric S %A Meyerson, Matthew %K Adenocarcinoma %K Cell Line, Tumor %K Chromosome Deletion %K Chromosomes, Human, Pair 14 %K Gene Amplification %K Genome, Human %K Genomics %K Genotype %K Humans %K Intracellular Signaling Peptides and Proteins %K Loss of Heterozygosity %K Lung Neoplasms %K Neoplasms %K Nuclear Proteins %K Polymorphism, Single Nucleotide %K Proto-Oncogene Mas %K RNA Interference %K Thyroid Nuclear Factor 1 %K Transcription Factors %X

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.

%B Nature %V 450 %P 893-8 %8 2007 Dec 06 %G eng %N 7171 %1 https://www.ncbi.nlm.nih.gov/pubmed/17982442?dopt=Abstract %R 10.1038/nature06358