Characterizing the cancer genome in lung adenocarcinoma.
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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. |
Year of Publication | 2007
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Journal | Nature
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Volume | 450
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Issue | 7171
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Pages | 893-8
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Date Published | 2007 Dec 06
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ISSN | 1476-4687
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URL | |
DOI | 10.1038/nature06358
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PubMed ID | 17982442
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PubMed Central ID | PMC2538683
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Grant list | F32 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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