Characterizing the cancer genome in lung adenocarcinoma

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 & 50 others 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 D. 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 G W 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

Research output: Contribution to journalArticle

811 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)893-898
Number of pages6
JournalNature
Volume450
Issue number7171
DOIs
StatePublished - Dec 6 2007

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Genome
Chromosomes
Neoplasms
Proto-Oncogenes
Homeobox Genes
Genes
Single Nucleotide Polymorphism
Transcription Factors
Carcinoma
Lung
Mutation
DNA
Adenocarcinoma of lung
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Weir, B. A., Woo, M. S., Getz, G., Perner, S., Ding, L., Beroukhim, R., ... Meyerson, M. (2007). Characterizing the cancer genome in lung adenocarcinoma. Nature, 450(7171), 893-898. https://doi.org/10.1038/nature06358

Characterizing the cancer genome in lung adenocarcinoma. / 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.

In: Nature, Vol. 450, No. 7171, 06.12.2007, p. 893-898.

Research output: Contribution to journalArticle

Weir, BA, Woo, MS, Getz, G, Perner, S, Ding, L, Beroukhim, R, Lin, WM, Province, MA, Kraja, A, Johnson, LA, Shah, K, Sato, M, Thomas, RK, Barletta, JA, Borecki, IB, Broderick, S, Chang, AC, Chiang, DY, Chirieac, LR, Cho, J, Fujii, Y, Gazdar, AF, Giordano, T, Greulich, H, Hanna, M, Johnson, BE, Kris, MG, Lash, A, Lin, L, Lindeman, N, Mardis, ER, McPherson, JD, Minna, JD, Morgan, MB, Nadel, M, Orringer, MB, Osborne, JR, Ozenberger, B, Ramos, AH, Robinson, J, Roth, JA, Rusch, V, Sasaki, H, Shepherd, F, Sougnez, C, Spitz, MR, Tsao, MS, Twomey, D, Verhaak, RGW, Weinstock, GM, Wheeler, DA, Winckler, W, Yoshizawa, A, Yu, S, Zakowski, MF, Zhang, Q, Beer, DG, Wistuba, II, Watson, MA, Garraway, LA, Ladanyi, M, Travis, WD, Pao, W, Rubin, MA, Gabriel, SB, Gibbs, RA, Varmus, HE, Wilson, RK, Lander, ES & Meyerson, M 2007, 'Characterizing the cancer genome in lung adenocarcinoma', Nature, vol. 450, no. 7171, pp. 893-898. https://doi.org/10.1038/nature06358
Weir BA, Woo MS, Getz G, Perner S, Ding L, Beroukhim R et al. Characterizing the cancer genome in lung adenocarcinoma. Nature. 2007 Dec 6;450(7171):893-898. https://doi.org/10.1038/nature06358
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. / Characterizing the cancer genome in lung adenocarcinoma. In: Nature. 2007 ; Vol. 450, No. 7171. pp. 893-898.
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