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. Olshan; Scott H. Randell; Fred A. Wright; Carol G. Shores; D. Neil Hayes

doi:10.1371/journal.pone.0056823

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

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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 language	English (US)
Article number	e56823
Journal	PloS one
Volume	8
Issue number	2
DOIs	https://doi.org/10.1371/journal.pone.0056823
State	Published - Feb 22 2013
Externally published	Yes

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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), Article e56823. https://doi.org/10.1371/journal.pone.0056823

Walter, V, Yin, X, Wilkerson, MD, Cabanski, CR, Zhao, N, Du, Y, Ang, MK, Hayward, MC, Salazar, AH, Hoadley, KA, Fritchie, K, Sailey, CG, Weissler, MC, Shockley, WW, Zanation, AM, Hackman, T, Thorne, LB, Funkhouser, WD, Muldrew, KL, Olshan, AF, Randell, SH, Wright, FA, Shores, CG & Hayes, DN 2013, 'Molecular Subtypes in Head and Neck Cancer Exhibit Distinct Patterns of Chromosomal Gain and Loss of Canonical Cancer Genes', PloS one, vol. 8, no. 2, e56823. https://doi.org/10.1371/journal.pone.0056823

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

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.",

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

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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.

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

Abstract

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