Lessons learned from next-generation sequencing in head and neck cancer.
Scientific innovation has enabled whole exome capture and massively parallel sequencing of cancer genomes. In head and neck cancer, next-generation sequencing has granted us further understanding of the mutational spectrum of squamous cell carcinoma. As a result of these new technologies, frequently occurring mutations were identified in NOTCH1, a gene that had not previously been implicated in head and neck cancer. The current review describes the most common mutations in head and neck cancer: TP53, NOTCH1, HRAS, PIK3CA, and CDKN2A. Emphasis is placed on the involved cellular pathways, clinical correlations, and potential therapeutic interventions. Additionally, the implications of human papillomavirus on mutation patterns are discussed.
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Myriam
M
Loyo
Ryan J
RJ
Li
Chetan
C
Bettegowda
Curtis R
CR
Pickering
Mitchell J
MJ
Frederick
Jeffrey N
JN
Myers
Nishant
N
Agrawal
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics; D000077195:Squamous Cell Carcinoma of Head and Neck; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D019941:Cyclin-Dependent Kinase Inhibitor p16; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)