title: Clinical, genomic, and metagenomic characterization of oral tongue squamous cell carcinoma in patients who do not smoke.
abstract: BACKGROUND
  Evidence suggests the incidence of oral tongue squamous cell carcinoma is increasing in young patients, many who have no history of tobacco use.
  
  
  METHODS
  We clinically reviewed 89 patients with oral tongue cancer. Exomic sequencing of tumor DNA from 6 nonsmokers was performed and compared to previously sequenced cases. RNA from 20 tumors was evaluated by massively parallel sequencing to search for potentially oncogenic viruses.
  
  
  RESULTS
  Non-smokers (53 of 89) were younger than smokers (36 of 89; mean, 50.4 vs 61.9 years; p < .001), and seemed more likely to be women (58.5% vs 38.9%; p = .069). Nonsmokers had fewer TP53 mutations (p = .02) than smokers. No tumor-associated viruses were detected.
  
  
  CONCLUSIONS
  The young age of nonsmoking patients with oral tongue cancer and fewer TP53 mutations suggest a viral role in this disease. Our efforts to identify such a virus were unsuccessful. Further studies are warranted to elucidate the drivers of carcinogenesis in these patients.
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Ryan
authors: R
authors: Li
authors: Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, California.
authors: Daniel L
authors: DL
authors: Faden
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.|Milton J. Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland.
authors: Carole
authors: C
authors: Fakhry
authors: Department of Medicine, University of California San Francisco, San Francisco, California.
authors: Chaz
authors: C
authors: Langelier
authors: The Ludwig Center and the Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland.
authors: Yuchen
authors: Y
authors: Jiao
authors: The Ludwig Center and the Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland.
authors: Yuxuan
authors: Y
authors: Wang
authors: Department of Genetics, University of North Carolina, Chapel Hill, North Carolina.|Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
authors: Matthew D
authors: MD
authors: Wilkerson
authors: Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: Chandra Sekhar
authors: CS
authors: Pedamallu
authors: Department of Otolaryngology-Head and Neck Surgery, Ohio State University, Columbus, Ohio.
authors: Matthew
authors: M
authors: Old
authors: Department of Otolaryngology-Head and Neck Surgery, Ohio State University, Columbus, Ohio.
authors: James
authors: J
authors: Lang
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Myriam
authors: M
authors: Loyo
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Sun Mi
authors: SM
authors: Ahn
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Marietta
authors: M
authors: Tan
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Zhen
authors: Z
authors: Gooi
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Jason
authors: J
authors: Chan
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Jeremy
authors: J
authors: Richmon
authors: Department of Pathology, Johns Hopkins University, Baltimore, Maryland.
authors: Laura D
authors: LD
authors: Wood
authors: Department of Pathology, Johns Hopkins University, Baltimore, Maryland.
authors: Ralph H
authors: RH
authors: Hruban
authors: Department of Pathology, Johns Hopkins University, Baltimore, Maryland.
authors: Justin
authors: J
authors: Bishop
authors: Department of Pathology, Johns Hopkins University, Baltimore, Maryland.
authors: William H
authors: WH
authors: Westra
authors: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Christine H
authors: CH
authors: Chung
authors: Milton J. Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland.
authors: Joseph
authors: J
authors: Califano
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Christine G
authors: CG
authors: Gourin
authors: Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Chetan
authors: C
authors: Bettegowda
authors: Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.|Department of Pathology, Harvard Medical School, Boston, Massachusetts.
authors: Matthew
authors: M
authors: Meyerson
authors: The Ludwig Center and the Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland.
authors: Nickolas
authors: N
authors: Papadopoulos
authors: The Ludwig Center and the Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland.
authors: Kenneth W
authors: KW
authors: Kinzler
authors: The Ludwig Center and the Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland.
authors: Bert
authors: B
authors: Vogelstein
authors: Howard Hughes Medical Institute, Chevy Chase, Maryland.|Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California.
authors: Joseph L
authors: JL
authors: DeRisi
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Wayne M
authors: WM
authors: Koch
authors: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.|The Ludwig Center and the Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland.
authors: Nishant
authors: N
authors: Agrawal
mesh_terms: D000328:Adult; D017677:Age Distribution; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D004273:DNA, Neoplasm / Q000235:genetics*; D016208:Databases, Factual; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D023281:Genomics; D006801:Humans; D015994:Incidence; D008297:Male; D054892:Metagenome / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D018570:Risk Assessment; D017678:Sex Distribution; D012907:Smoking; D014062:Tongue Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: head and neck cancer; next-generation sequencing; nonsmokers; oral tongue; squamous cell carcinoma