Comprehensive molecular profiling of lung adenocarcinoma

Nature. 511: p543-550, 31 July 2014 10.1038/nature13385

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.

Data in the GDC

• GDC Manifests
  • Open-Access Data - Download Manifest (13 Files)
  • Controlled-Access Data - Download Manifest (4 Files) | WGS Files (1 File)

Supplemental Files

• Supplementary Material - Contents:
  • Pathology
  • DNA sequencing, validation, and data processing
  • Transversion high/low analysis
  • Copy number analysis and low-pass whole genome sequencing
  • RNA sequencing
    • MAF with RNA confirmation
    • Expression Matrix
    • Expression Subtype Calls
    • RNA Fusion Detections
  • RNA splicing
  • Oncogene discovery analysis
  • Reverse-phase protein array data
  • microRNA sequencing analysis
  • DNA methylation
  • iCluster analysis

Supplemental Data

• Sample Lists
  • Cumulative Sample List [txt]
• Mutations
  • Publication MAF
  • Publication MAF MAGE-TAB
• Additional MAF files
  • AN_TCGA_LUAD_PAIR_capture_freeze_FINAL_230.09_04_13.maf
  • AN_TCGA_LUAD_PAIR_capture_freeze_FINAL_230.09_04_13.maf.md5
  • AN_TCGA_LUAD_PAIR_capture_freeze_FINAL_230.09_04_13.with_CIP.maf
  • AN_TCGA_LUAD_PAIR_capture_freeze_FINAL_230.09_04_13.with_CIP.maf.md5
• Copy Number
  •  
  •  
  •  
  •  
  •  
  •  
  • GISTIC marker file [lst.gz]
• Exome Sequence BAM File References
  • BAM sequence files [xlsx]
• Clinical
  • Open-access clinical data [xlsx]

Additional Resources

• GDC Encyclopedia
• Descriptions of TCGA data are provided in the TCGA Barcode Encyclopedia Page
• Genomic Data Commons Portal