Comprehensive molecular profiling of lung adenocarcinoma: the cancer genome atlas research network

The Cancer Genome Atlas Research Network, Duhig, Edwina, Clarke, Belinda, Yang, Ian A., Fong, Kwun M., Hunter, Lindy, Windsor, Morgan and Bowman, Rayleen V. (2014) Comprehensive molecular profiling of lung adenocarcinoma: the cancer genome atlas research network. Nature, 511 7511: 543-550. doi:10.1038/nature13385


Author The Cancer Genome Atlas Research Network
Duhig, Edwina
Clarke, Belinda
Yang, Ian A.
Fong, Kwun M.
Hunter, Lindy
Windsor, Morgan
Bowman, Rayleen V.
Title Comprehensive molecular profiling of lung adenocarcinoma: the cancer genome atlas research network
Journal name Nature   Check publisher's open access policy
ISSN 1476-4687
0028-0836
Publication date 2014-07-09
Year available 2014
Sub-type Article (original research)
DOI 10.1038/nature13385
Open Access Status DOI
Volume 511
Issue 7511
Start page 543
End page 550
Total pages 8
Place of publication London United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.
Keyword Multidisciplinary Sciences
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID U24 CA126561
U24 CA143867
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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