TY - JOUR
T1 - Molecular Subtypes in Head and Neck Cancer Exhibit Distinct Patterns of Chromosomal Gain and Loss of Canonical Cancer Genes
AU - Walter, Vonn
AU - Yin, Xiaoying
AU - Wilkerson, Matthew D.
AU - Cabanski, Christopher R.
AU - Zhao, Ni
AU - Du, Ying
AU - Ang, Mei Kim
AU - Hayward, Michele C.
AU - Salazar, Ashley H.
AU - Hoadley, Katherine A.
AU - Fritchie, Karen
AU - Sailey, Charles G.
AU - Weissler, Mark C.
AU - Shockley, William W.
AU - Zanation, Adam M.
AU - Hackman, Trevor
AU - Thorne, Leigh B.
AU - Funkhouser, William D.
AU - Muldrew, Kenneth L.
AU - Olshan, Andrew F.
AU - Randell, Scott H.
AU - Wright, Fred A.
AU - Shores, Carol G.
AU - Hayes, D. Neil
PY - 2013/2/22
Y1 - 2013/2/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84874327940&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0056823
DO - 10.1371/journal.pone.0056823
M3 - Article
AN - SCOPUS:84874327940
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 2
M1 - e56823
ER -