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Home > Publications > Comprehensive molecular profiling of lung adenocarcinoma, 2014

Comprehensive molecular profiling of lung adenocarcinoma

Nature, Volumn 511,Issue 7511, Page 543-550 [doi:10.1038/nature13385]

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 that 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.

Associated Data Files

Sample Lists

  • Cumulative Sample List [txt]
  • Mutations

    Expression

    Copy Number

    miRNA Expression

    Methylation

    Reverse-phase Protein Array

  • RPPA Level 1 [tar.gz]
  • RPPA Level 2 [tar.gz]
  • RPPA Level 3 [tar.gz]
  • RPPA MAGE-TAB [tar.gz]
  • Exome Sequence BAM File References

  • BAM sequence files available at CGHub [xlsx]
  • Clinical

  • Open-access clinical data [xlsx]
  • Supplementary Files

  • Supplementary Material - Contents:
  • Additional Information