Characterizing the cancer genome in lung adenocarcinoma.

TitleCharacterizing the cancer genome in lung adenocarcinoma.
Publication TypeJournal Article
Year of Publication2007
AuthorsWeir, 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, M-S, 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
Date Published2007 Dec 06
KeywordsAdenocarcinoma, Cell Line, Tumor, Chromosome Deletion, Chromosomes, Human, Pair 14, Gene Amplification, Genome, Human, Genomics, Genotype, Humans, Intracellular Signaling Peptides and Proteins, Loss of Heterozygosity, Lung Neoplasms, Neoplasms, Nuclear Proteins, Polymorphism, Single Nucleotide, Proto-Oncogene Mas, RNA Interference, Thyroid Nuclear Factor 1, Transcription Factors

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.

Alternate JournalNature
PubMed ID17982442
PubMed Central IDPMC2538683
Grant ListF32 CA113126-01A1 / CA / NCI NIH HHS / United States
F32 CA113126-02 / CA / NCI NIH HHS / United States
K08 CA122833-01A1 / CA / NCI NIH HHS / United States
P50 CA070907 / CA / NCI NIH HHS / United States

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