Novel insight into mutational landscape of head and neck squamous cell carcinoma

• Published in: PloS one 2014-03, Vol.9 (3), p.e93102
• Main Authors: Gaykalova, Daria A, Mambo, Elizabeth, Choudhary, Ashish, Houghton, Jeffery, Buddavarapu, Kalyan, Sanford, Tiffany, Darden, Will, Adai, Alex, Hadd, Andrew, Latham, Gary, Danilova, Ludmila V, Bishop, Justin, Li, Ryan J, Westra, William H, Hennessey, Patrick, Koch, Wayne M, Ochs, Michael F, Califano, Joseph A, Sun, Wenyue
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alterations; Analysis; Biology and Life Sciences; Cancer; Cancer genetics; Cancer therapies; Carcinogenesis; Carcinogens; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Deoxyribonucleic acid; DNA; DNA Mutational Analysis; Epigenetics; Fibroblast growth factor receptors; Gene amplification; Gene frequency; Gene sequencing; Genes; Genetic aspects; Genetics; Head & neck cancer; Head and neck cancer; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - pathology; Health aspects; Human papillomavirus; Humans; Informatics; Kinases; Leukemia; Medicine and Health Sciences; Middle Aged; Mortality; Mutation; Notch protein; Notch1 protein; Otolaryngology; p53 Protein; Papillomavirus infections; Pathology; Patients; Science; Signal transduction; Signaling; Smoking; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Surgery; Tissues; Tumor proteins; Tumor suppressor genes; Tumorigenesis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0093102

Development of head and neck squamous cell carcinoma (HNSCC) is characterized by accumulation of mutations in several oncogenes and tumor suppressor genes. We have formerly described the mutation pattern of HNSCC and described NOTCH signaling pathway alterations. Given the complexity of the HNSCC, here we extend the previous study to understand the overall HNSCC mutation context and to discover additional genetic alterations. We performed high depth targeted exon sequencing of 51 highly actionable cancer-related genes with a high frequency of mutation across many cancer types, including head and neck. DNA from primary tumor tissues and matched normal tissues was analyzed for 37 HNSCC patients. We identified 26 non-synonymous or stop-gained mutations targeting 11 of 51 selected genes. These genes were mutated in 17 out of 37 (46%) studied HNSCC patients. Smokers harbored 3.2-fold more mutations than non-smokers. Importantly, TP53 was mutated in 30%, NOTCH1 in 8% and FGFR3 in 5% of HNSCC. HPV negative patients harbored 4-fold more TP53 mutations than HPV positive patients. These data confirm prior reports of the HNSCC mutational profile. Additionally, we detected mutations in two new genes, CEBPA and FES, which have not been previously reported in HNSCC. These data extend the spectrum of HNSCC mutations and define novel mutation targets in HNSCC carcinogenesis, especially for smokers and HNSCC without HPV infection.