Ryan Li1, Daniel L Faden2, Carole Fakhry1,3, Chaz Langelier4, Yuchen Jiao5, Yuxuan Wang5, Matthew D Wilkerson6,7, Chandra Sekhar Pedamallu8,9, Matthew Old10, James Lang10, Myriam Loyo1, Sun Mi Ahn1, Marietta Tan1, Zhen Gooi1, Jason Chan1, Jeremy Richmon1, Laura D Wood11, Ralph H Hruban11, Justin Bishop11, William H Westra11, Christine H Chung12, Joseph Califano3, Christine G Gourin1, Chetan Bettegowda13, Matthew Meyerson8,9,14, Nickolas Papadopoulos5, Kenneth W Kinzler5, Bert Vogelstein5, Joseph L DeRisi15,16, Wayne M Koch1, Nishant Agrawal1,5. 1. Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. 2. Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, California. 3. Milton J. Dance Head and Neck Center, Greater Baltimore Medical Center, Baltimore, Maryland. 4. Department of Medicine, University of California San Francisco, San Francisco, California. 5. The Ludwig Center and the Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland. 6. Department of Genetics, University of North Carolina, Chapel Hill, North Carolina. 7. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina. 8. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts. 9. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. 10. Department of Otolaryngology-Head and Neck Surgery, Ohio State University, Columbus, Ohio. 11. Department of Pathology, Johns Hopkins University, Baltimore, Maryland. 12. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland. 13. Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. 14. Department of Pathology, Harvard Medical School, Boston, Massachusetts. 15. Howard Hughes Medical Institute, Chevy Chase, Maryland. 16. Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California.
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. CONCLUSION: 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.
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. CONCLUSION: 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.
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