uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Somatic mutations affect key pathways in lung adenocarcinoma
Show others and affiliations
2008 (English)In: Nature, ISSN 0028-0836, Vol. 455, no 7216, 1069-1075 p.Article in journal (Refereed) Published
Abstract [en]

Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.

Place, publisher, year, edition, pages
2008. Vol. 455, no 7216, 1069-1075 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-100853DOI: 10.1038/nature07423ISI: 000260252600036PubMedID: 18948947OAI: oai:DiVA.org:uu-100853DiVA: diva2:211129
Available from: 2009-04-08 Created: 2009-04-08 Last updated: 2011-03-18Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Department of Medical Biochemistry and Microbiology
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 249 hits
ReferencesLink to record
Permanent link

Direct link