DNA copy number alterations (CNAs) are frequent in
cancer, and recently developed CNA signatures revealed their value in molecular
tumor stratification for patient prognosis and
platinum resistance prediction in
ovarian cancer.
Head and neck squamous cell carcinoma (
HNSCC) is also characterized by high CNAs. In this study, we determined CNA in 173 human papilloma virus-negative
HNSCC from a Dutch multicenter cohort by low-coverage whole genome sequencing and tested the prognostic value of seven
cancer-derived CNA signatures for these
cisplatin- and
radiotherapy-treated patients. We find that a high CNA signature 1 (s1) score is associated with low values for all other signatures and better patient outcomes in the Dutch cohorts and The
Cancer Genome Atlas
HNSCC data set. High s5 and s7 scores are associated with increased distant
metastasis rates and high s6 scores with poor overall survival. High cumulative
cisplatin doses result in improved outcomes in
chemoradiotherapy-treated
HNSCC patients. Here we find that
tumors high in s1 or low in s6 are most responsive to a change in
cisplatin dose. High s5 values, however, significantly increase the risk for
metastasis in patients with low cumulative
cisplatin doses. Together this suggests that the processes causing these CNA signatures affect
cisplatin response in
HNSCC. In conclusion, CNA signatures derived from a different
cancer type were prognostic and associated with
cisplatin response in
HNSCC, suggesting they represent underlying molecular processes that define patient outcome.