Authors: | Weir, B. A.; Woo, M. S.; Getz, G.; Perner, S.; Ding, L.; Beroukhim, R.; Lin, W. M.; Province, M. A.; Kraja, A.; Johnson, L. A.; Shah, K.; Sato, M.; Thomas, R. K.; Barletta, J. A.; Borecki, I. B.; Broderick, S.; Chang, A. C.; Chiang, D. Y.; Chirieac, L. R.; Cho, J.; Fujii, Y.; Gazdar, A. F.; Giordano, T.; Greulich, H.; Hanna, M.; Johnson, B. E.; Kris, M. G.; Lash, A.; Lin, L.; Lindeman, N.; Mardis, E. R.; McPherson, J. D.; Minna, J. D.; Morgan, M. B.; Nadel, M.; Orringer, M. B.; Osborne, J. R.; Ozenberger, B.; Ramos, A. H.; Robinson, J.; Roth, J. A.; Rusch, V.; Sasaki, H.; Shepherd, F.; Sougnez, C.; Spitz, M. R.; Tsao, M. S.; Twomey, D.; Verhaak, R. G. W.; Weinstock, G. M.; Wheeler, D. A.; Winckler, W.; Yoshizawa, A.; Yu, S.; Zakowski, M. F.; Zhang, Q.; Beer, D. G.; Wistuba, I. I.; Watson, M. A.; Garraway, L. A.; Ladanyi, M.; Travis, W. D.; Pao, W.; Rubin, M. A.; Gabriel, S. B.; Gibbs, R. A.; Varmus, H. E.; Wilson, R. K.; Lander, E. S.; Meyerson, M. |
Article Title: | Characterizing the cancer genome in lung adenocarcinoma |
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 ∼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. ©2007 Nature Publishing Group. |
Keywords: | human tissue; unclassified drug; gene mutation; single nucleotide polymorphism; gene deletion; mutation; polymorphism, single nucleotide; cancer recurrence; genetic analysis; neoplasms; adenocarcinoma; chromosome; gene amplification; lung neoplasms; genotype; transcription factor; rna interference; cell line, tumor; transcription factors; nuclear proteins; genome analysis; homozygosity; oncogene; lung adenocarcinoma; dna; intracellular signaling peptides and proteins; genomics; genome; lung carcinoma; tumor; loss of heterozygosity; chromosome deletion; genome, human; chromosome 14q; respiratory disease; array; chromosomes, human, pair 14; nk2 homeobox 1 protein |
Journal Title: | Nature |
Volume: | 450 |
Issue: | 7171 |
ISSN: | 0028-0836 |
Publisher: | Nature Publishing Group |
Date Published: | 2007-12-06 |
Start Page: | 893 |
End Page: | 898 |
Language: | English |
DOI: | 10.1038/nature06358 |
PUBMED: | 17982442 |
PROVIDER: | scopus |
PMCID: | PMC2538683 |
DOI/URL: | |
Notes: | --- - "Cited By (since 1996): 323" - "Export Date: 17 November 2011" - "CODEN: NATUA" - "Source: Scopus" |