Comprehensive molecular profiling of lung adenocarcinoma Journal Article


Author: The Cancer Genome Atlas Research Network
Contributors: Lee, W.; Askoy, B. A.; Ciriello, G.; Taylor, B. S.; Dresdner, G.; Gao, J.; Gross, B.; Seshan, V. E.; Ladanyi, M.; Reva, B.; Sinha, R.; Sumer, S. O.; Weinhold, N.; Schultz, N.; Shen, R.; Sander, C.; Travis, W. D.; Rekhtman, N.; Zakowski, M.; Rusch, V. W.
Article Title: Comprehensive molecular profiling of lung adenocarcinoma
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. © 2014 Macmillan Publishers Limited. All rights reserved.
Keywords: mitogen activated protein kinase; human tissue; protein expression; major clinical study; somatic mutation; exon; gene; microrna; gene amplification; gene expression profiling; lung resection; proteomics; dna methylation; molecular mechanics; chromosome aberration; oncogene; gene activation; lung adenocarcinoma; messenger rna; chromosome rearrangement; dna sequence; egfr gene; gender; concentration (parameters); loss of function mutation; oncogene myc; rna sequence; copy number variation; met gene; nf1 gene; erbb2 gene; human; male; female; priority journal; article; rbm10 gene; rit1 gene
Journal Title: Nature
Volume: 511
Issue: 7511
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2014-07-31
Start Page: 543
End Page: 550
Language: English
DOI: 10.1038/nature13385
PROVIDER: scopus
PUBMED: 25079552
PMCID: PMC4231481
DOI/URL:
Notes: Export Date: 2 September 2014 -- CODEN: NATUA -- Source: Scopus
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MSK Authors
  1. Venkatraman Ennapadam Seshan
    285 Seshan
  2. Natasha Rekhtman
    210 Rekhtman
  3. Valerie W Rusch
    651 Rusch
  4. Ronglai Shen
    127 Shen
  5. Marc Ladanyi
    861 Ladanyi
  6. William D Travis
    548 Travis
  7. Maureen F Zakowski
    275 Zakowski
  8. Boris A Reva
    36 Reva
  9. Chris Sander
    196 Sander
  10. Rileen Sinha
    19 Sinha
  11. Jianjiong Gao
    62 Gao
  12. Barry Stephen Taylor
    138 Taylor
  13. Nikolaus D Schultz
    196 Schultz
  14. Benjamin E Gross
    26 Gross
  15. William Lee
    38 Lee
  16. Bulent Arman Aksoy
    33 Aksoy
  17. Selcuk Onur Sumer
    21 Sumer