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.
authors: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors: Vonn
authors: V
authors: Walter
authors: Xiaoying
authors: X
authors: Yin
authors: Matthew D
authors: MD
authors: Wilkerson
authors: Christopher R
authors: CR
authors: Cabanski
authors: Ni
authors: N
authors: Zhao
authors: Ying
authors: Y
authors: Du
authors: Mei Kim
authors: MK
authors: Ang
authors: Michele C
authors: MC
authors: Hayward
authors: Ashley H
authors: AH
authors: Salazar
authors: Katherine A
authors: KA
authors: Hoadley
authors: Karen
authors: K
authors: Fritchie
authors: Charles J
authors: CJ
authors: Sailey
authors: Charles G
authors: CG
authors: Sailey
authors: Mark C
authors: MC
authors: Weissler
authors: William W
authors: WW
authors: Shockley
authors: Adam M
authors: AM
authors: Zanation
authors: Trevor
authors: T
authors: Hackman
authors: Leigh B
authors: LB
authors: Thorne
authors: William D
authors: WD
authors: Funkhouser
authors: Kenneth L
authors: KL
authors: Muldrew
authors: Andrew F
authors: AF
authors: Olshan
authors: Scott H
authors: SH
authors: Randell
authors: Fred A
authors: FA
authors: Wright
authors: Carol G
authors: CG
authors: Shores
authors: D Neil
authors: DN
authors: Hayes
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002869:Chromosome Aberrations; D058534:Class I Phosphatidylinositol 3-Kinases; D019938:Cyclin D1 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000072019:Kelch-Like ECH-Associated Protein 1; D008297:Male; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C530104:CCND1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors