The mutational landscape of head and neck squamous cell carcinoma Academic Article uri icon


MeSH Major

  • Carcinoma
  • Head and Neck Neoplasms
  • Mutation
  • Neoplasms, Squamous Cell
  • Receptor, Notch1
  • Sequence Analysis, DNA


  • Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), our analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis. More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms.


publication date

  • August 26, 2011



  • Academic Article



  • eng

PubMed Central ID

  • PMC3415217

Digital Object Identifier (DOI)

  • 10.1126/science.1208130

PubMed ID

  • 21798893

Additional Document Info

start page

  • 1157

end page

  • 60


  • 333


  • 6046