title: Novel insight into mutational landscape of head and neck squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Daria A
authors.initials: DA
authors.lastname: Gaykalova
authors.affiliation: Asuragen Inc., Austin, Texas, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mambo
authors.affiliation: Asuragen Inc., Austin, Texas, United States of America.
authors.forename: Ashish
authors.initials: A
authors.lastname: Choudhary
authors.affiliation: Asuragen Inc., Austin, Texas, United States of America.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Houghton
authors.affiliation: Asuragen Inc., Austin, Texas, United States of America.
authors.forename: Kalyan
authors.initials: K
authors.lastname: Buddavarapu
authors.affiliation: Asuragen Inc., Austin, Texas, United States of America.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Sanford
authors.affiliation: Asuragen Inc., Austin, Texas, United States of America.
authors.forename: Will
authors.initials: W
authors.lastname: Darden
authors.affiliation: Asuragen Inc., Austin, Texas, United States of America.
authors.forename: Alex
authors.initials: A
authors.lastname: Adai
authors.affiliation: Asuragen Inc., Austin, Texas, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hadd
authors.affiliation: Asuragen Inc., Austin, Texas, United States of America.
authors.forename: Gary
authors.initials: G
authors.lastname: Latham
authors.affiliation: Department of Oncology and Health Science Informatics, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Ludmila V
authors.initials: LV
authors.lastname: Danilova
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Justin
authors.initials: J
authors.lastname: Bishop
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Li
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hennessey
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Koch
authors.affiliation: Department of Oncology and Health Science Informatics, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Ochs
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America; Milton J. Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland, United States of America.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Wenyue
authors.initials: W
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D000077195:Squamous Cell Carcinoma of Head and Neck