Journal Article

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

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

2013

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aged / Analysis / Bioinformatics / Biology / Cancer / Cancer genetics / Carcinoma, Squamous Cell - genetics / Cell adhesion & migration / Chromosome Aberrations / Class I Phosphatidylinositol 3-Kinases / Copy number / Cyclin D1 - genetics / Deregulation / DNA Copy Number Variations - genetics / Epidermal growth factor receptors / ErbB Receptors - genetics / Etiology / Female / Gene expression / Genes / Genetic aspects / Genetic research / Genomic analysis / Head / Head & neck cancer / Head and neck cancer / Head and Neck Neoplasms - genetics / Health aspects / Human papillomavirus / Humans / Intracellular Signaling Peptides and Proteins - genetics / Kelch-Like ECH-Associated Protein 1 / Kinases / Laboratories / Lung carcinoma / Male / Medicine / Mesenchyme / Middle Aged / NF-E2-Related Factor 2 - genetics / Otolaryngology / Oxidative stress / Papillomavirus infections / Pathology / Phosphatidylinositol 3-Kinases - genetics / Signatures / SOXB1 Transcription Factors - genetics / Squamous cell carcinoma / Squamous Cell Carcinoma of Head and Neck / Statistical analysis / Stem cells / Survival analysis / Transcription Factors - genetics / Tumor Suppressor Proteins - genetics / Tumors / Viruses