Comprehensive genomic characterization of squamous cell lung cancers

Nature. 489: p519-525, 9 September 2012 10.1038/nature11404

Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers.

Data in the GDC

• GDC Manifests
  • Open-Access Data - Download Manifest (41 Files)
  • Controlled-Access Data - Download Manifest (5 Files)

Supplemental Data

• Sample Lists
  • Cumulative Sample List [xlsx|html]
• Mutations
  • Somatic MAF archive [.gz]
• Expression
  • Agilent microarray Level 1 [tar]
  • Agilent microarray Level 2 [tar]
  • Agilent microarray Level 3 [tar]
  • RNASeq Level 3 [tar.gz]
• Copy Number
  • Affymetrix SNP6 Level 1 [tar]
  • Affymetrix SNP6 Level 2 [tar]
  • Affymetrix SNP6 Level 3 [tar]
  • Agilent aCGH 415K Level 1 [tar]
  • Agilent aCGH 415K Level 2 [tar]
  • Agilent aCGH 415K Level 3 [tar]
  • Agilent aCGH 1M Level 1 [tar]
  • Agilent aCGH 1M Level 2 [tar]
  • Agilent aCGH 1M Level 3 [tar]
  • GISTIC marker file [lst.gz]
• miRNA Expression
  • miRNASeq Level 3 [tar]
  • miRNASeq BAM File list [txt]
• Methylation
  • Infinium Human Methylation HM27 and HM450 Level 1 [tar]
  • Infinium Human Methylation HM27 and HM450 Level 2 [tar]
  • Infinium Human Methylation HM27 and HM450 Level 3 [tar]
• DNA Sequence BAM File References
  • DNA Sequence BAM Freeze List [txt]
• Clinical
  • Open-access clinical data [xlsx|html]

Supplementary Files

• GISTIC Amplification Peak Annotations [txt] (Data File S2.1)
• GISTIC Deletion Peak Annotations [txt] (Data File S2.2)
• Whole Genome Rearrangements [txt] (Data File S3.1)
• RNASeq Annotated RPKM Values [csv.zip] (Supplementary Methods S4: RNA Sequencing)
• RNA Fusion Confirmation of DNA Breakpoints [xlsx|html] (Data File S4.1)
• RNA Fusion Predictions [xlsx|html] (Data File S4.2)
• RNA Annotated Sequence Mutation Files [csv.zip] (Data File S4.3)
• Hypermethylated Loci [xlsx|html] (Data File S6.1)
• Hypomethylated Loci [xlsx|html] (Data File S6.2)
• P16 Supplementary Data [xlsx|html] (Data File S7.1)
• Data for Figure 5 (Validated and candidate therapeutic targets are commonly altered in lung SqCCs) [xls|html] (Data File S7.2)
• Data for Figure 5a (Heatmap representation of the number of somatic mutations by protein class)
• Data for Figure 5b (Mutations and amplifications in selected genes) [xlsx|html] (Data File S7.4)

Additional Resources

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