Comprehensive molecular profiling of lung adenocarcinoma
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Lander_Comprehensive molecular.pdf
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1.37 MB
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22e840050d5ac597e6480e8768da68ee
Author(s)
Lander, Eric Steven
Date Issued
July 2014
Journal
Nature
Publisher
Nature Publishing Group
Citation
Collisson, Eric A., Joshua D. Campbell, Angela N. Brooks, Alice H. Berger, William Lee, Juliann Chmielecki, David G. Beer, et al. “Comprehensive Molecular Profiling of Lung Adenocarcinoma.” Nature 511, no. 7511 (July 9, 2014): 543–550.
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1038/nature13385
