Molecular Subtypes in Head and Neck Cancer Exhibit Distinct Patterns of Chromosomal Gain and Loss of Canonical Cancer Genes

Vonn Walter, Xiaoying Yin, Matthew D. Wilkerson, Christopher R. Cabanski, Ni Zhao, Ying Du, Mei Kim Ang, Michele C. Hayward, Ashley H. Salazar, Katherine A. Hoadley, Karen Fritchie, Charles G. Sailey, Mark C. Weissler, William W. Shockley, Adam M. Zanation, Trevor Hackman, Leigh B. Thorne, William D. Funkhouser, Kenneth L. Muldrew, Andrew F. OlshanScott H. Randell, Fred A. Wright, Carol G. Shores, D. Neil Hayes

Research output: Contribution to journalArticle

144 Scopus citations

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal heterogeneous disease. Beyond the role of human papilloma virus (HPV), no validated molecular characterization of the disease has been established. Using an integrated genomic analysis and validation methodology we confirm four molecular classes of HNSCC (basal, mesenchymal, atypical, and classical) consistent with signatures established for squamous carcinoma of the lung, including deregulation of the KEAP1/NFE2L2 oxidative stress pathway, differential utilization of the lineage markers SOX2 and TP63, and preference for the oncogenes PIK3CA and EGFR. For potential clinical use the signatures are complimentary to classification by HPV infection status as well as the putative high risk marker CCND1 copy number gain. A molecular etiology for the subtypes is suggested by statistically significant chromosomal gains and losses and differential cell of origin expression patterns. Model systems representative of each of the four subtypes are also presented.

Original languageEnglish (US)
Article numbere56823
JournalPloS one
Volume8
Issue number2
DOIs
StatePublished - Feb 22 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Walter, V., Yin, X., Wilkerson, M. D., Cabanski, C. R., Zhao, N., Du, Y., Ang, M. K., Hayward, M. C., Salazar, A. H., Hoadley, K. A., Fritchie, K., Sailey, C. G., Weissler, M. C., Shockley, W. W., Zanation, A. M., Hackman, T., Thorne, L. B., Funkhouser, W. D., Muldrew, K. L., ... Hayes, D. N. (2013). Molecular Subtypes in Head and Neck Cancer Exhibit Distinct Patterns of Chromosomal Gain and Loss of Canonical Cancer Genes. PloS one, 8(2), [e56823]. https://doi.org/10.1371/journal.pone.0056823