Characterizing the cancer genome in lung adenocarcinoma
- PMID: 17982442
- PMCID: PMC2538683
- DOI: 10.1038/nature06358
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 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.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2538683/bin/nihms52941f1.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2538683/bin/nihms52941f2.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2538683/bin/nihms52941f3.gif)
Similar articles
-
KRAS and NKX2-1 Mutations in Invasive Mucinous Adenocarcinoma of the Lung.J Thorac Oncol. 2016 Apr;11(4):496-503. doi: 10.1016/j.jtho.2016.01.010. Epub 2016 Jan 30. J Thorac Oncol. 2016. PMID: 26829311
-
Collection, integration and analysis of cancer genomic profiles: from data to insight.Curr Opin Genet Dev. 2014 Feb;24:92-8. doi: 10.1016/j.gde.2013.12.003. Epub 2014 Feb 27. Curr Opin Genet Dev. 2014. PMID: 24584084 Free PMC article. Review.
-
NKX2-1/TTF-1: an enigmatic oncogene that functions as a double-edged sword for cancer cell survival and progression.Cancer Cell. 2013 Jun 10;23(6):718-23. doi: 10.1016/j.ccr.2013.04.002. Cancer Cell. 2013. PMID: 23763999 Review.
-
Suppression of lung adenocarcinoma progression by Nkx2-1.Nature. 2011 May 5;473(7345):101-4. doi: 10.1038/nature09881. Epub 2011 Apr 6. Nature. 2011. PMID: 21471965 Free PMC article.
-
Both gene amplification and allelic loss occur at 14q13.3 in lung cancer.Clin Cancer Res. 2011 Feb 15;17(4):690-9. doi: 10.1158/1078-0432.CCR-10-1892. Epub 2010 Dec 10. Clin Cancer Res. 2011. PMID: 21148747 Free PMC article.
Cited by
-
Adjuvant Novel Nanocarrier-Based Targeted Therapy for Lung Cancer.Molecules. 2024 Feb 29;29(5):1076. doi: 10.3390/molecules29051076. Molecules. 2024. PMID: 38474590 Free PMC article. Review.
-
Expanding Broad Molecular Reflex Testing in Non-Small Cell Lung Cancer to Squamous Histology.Cancers (Basel). 2024 Feb 23;16(5):903. doi: 10.3390/cancers16050903. Cancers (Basel). 2024. PMID: 38473263 Free PMC article.
-
Differentially Expressed Genes Involved in Primary Resistance to Immunotherapy in Patients with Advanced-Stage Pulmonary Cancer.Int J Mol Sci. 2024 Feb 8;25(4):2048. doi: 10.3390/ijms25042048. Int J Mol Sci. 2024. PMID: 38396726 Free PMC article.
-
ASCC3 promotes the immunosuppression and progression of non-small cell lung cancer by impairing the type I interferon response via CAND1-mediated ubiquitination inhibition of STAT3.J Immunother Cancer. 2023 Dec 26;11(12):e007766. doi: 10.1136/jitc-2023-007766. J Immunother Cancer. 2023. PMID: 38148115 Free PMC article.
-
Decoding the basis of histological variation in human cancer.Nat Rev Cancer. 2024 Feb;24(2):141-158. doi: 10.1038/s41568-023-00648-5. Epub 2023 Dec 22. Nat Rev Cancer. 2024. PMID: 38135758 Review.
References
-
- Weir B, Zhao X, Meyerson M. Somatic alterations in the human cancer genome. Cancer Cell. 2004;6:433–438. - PubMed
-
- Sawyers C. Targeted cancer therapy. Nature. 2004;432:294–297. - PubMed
-
- Pinkel D, et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nature Genet. 1998;20:207–211. - PubMed
-
- Pollack JR, et al. Genome-wide analysis of DNA copy-number changes using cDNA microarrays. Nature Genet. 1999;23:41–46. - PubMed
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials