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Mutational analysis of head and neck squamous cell carcinoma stratified by smoking status.
JCI Insight
  • Farhad Ghasemi, Western University
  • Stephenie D Prokopec, Western University
  • Danielle MacNeil, Western University
  • Neil Mundi, Western University
  • Steven F Gameiro, Western University
  • Christopher Howlett, Western University
  • William Stecho, Western University
  • Paul Plantinga, Western University
  • Nicole Pinto, Western University
  • Kara M Ruicci, Western University
  • Mohammed Imran Khan, Western University
  • John Yoo, Western University
  • Kevin Fung, Western University
  • Axel Sahovaler, Western University
  • David A Palma, Western University
  • Eric Winquist, Western University
  • Joe S Mymryk, Western University
  • John W Barrett, Western University
  • Paul C Boutros
  • Anthony C Nichols
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Smoking has historically been recognized as a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). This study aimed to assess the mutational differences between heavy smokers (>20 pack years) and never smokers among the HNSCC patients within The Cancer Genome Atlas (TCGA). Single nucleotide variation and copy number aberration differences between heavy smokers and never smokers were compared within human papillomavirus-positive (HPV-positive) (n = 67) and HPV-negative (n = 431) TCGA cohorts with HNSCC, and the impact of these mutations on survival were assessed. No genes were differentially mutated between smoking and never-smoking patients with HPV-positive tumors. By contrast, in HPV-negative tumors, NSD1 and COL1A11 were found to be more frequently mutated in heavy smokers, while CASP8 was more frequently altered in never smokers. HPV-negative patients with NSD1 mutations experienced significantly improved overall survival compared with NSD1 WT patients. This improved prognosis was validated in an independent cohort of 77 oral cavity cancer patients and a meta-analysis that included 2 additional data sets (688 total patients, hazard ratio for death 0.44, 95% CI, 0.30-0.65). NSD1 mutations are more common in HPV-negative heavy smokers, define a cohort with favorable prognosis, and may represent a clinically useful biomarker to guide treatment deintensification for HPV-negative patients.


Also available open access in JCI Insight V.4 No.1 at

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Citation Information
Farhad Ghasemi, Stephenie D Prokopec, Danielle MacNeil, Neil Mundi, et al.. "Mutational analysis of head and neck squamous cell carcinoma stratified by smoking status." JCI Insight Vol. 4 Iss. 1 (2019)
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