The mutational landscape of head and neck squamous cell carcinoma

Science. 2011 Aug 26;333(6046):1157-60. doi: 10.1126/science.1208130. Epub 2011 Jul 28.

Abstract

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 types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Apoptosis
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / virology
  • Carcinoma, Squamous Cell
  • Cell Differentiation
  • Exons
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / virology
  • Humans
  • Mutation*
  • Neoplasms, Squamous Cell / genetics*
  • Neoplasms, Squamous Cell / metabolism
  • Neoplasms, Squamous Cell / virology
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / virology
  • Point Mutation
  • Receptor, Notch1 / genetics*
  • Receptor, Notch1 / metabolism
  • Sequence Analysis, DNA*
  • Sequence Deletion
  • Signal Transduction
  • Smoking
  • Squamous Cell Carcinoma of Head and Neck
  • Tobacco

Substances

  • NOTCH1 protein, human
  • Receptor, Notch1