Somatic mutations affect key pathways in lung adenocarcinoma.

Nature
Authors
Keywords
Abstract

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.

Year of Publication
2008
Journal
Nature
Volume
455
Issue
7216
Pages
1069-75
Date Published
2008 Oct 23
ISSN
1476-4687
URL
DOI
10.1038/nature07423
PubMed ID
18948947
PubMed Central ID
PMC2694412
Links
Grant list
U54 HG003067 / HG / NHGRI NIH HHS / United States
U19 CA084953-050003 / CA / NCI NIH HHS / United States
U54 HG003067-04 / HG / NHGRI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
P50 CA070907 / CA / NCI NIH HHS / United States
U19 CA084953 / CA / NCI NIH HHS / United States
R01 CA154365 / CA / NCI NIH HHS / United States