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.

中文翻译：

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卵巢癌衍生的拷贝数改变特征对于放化疗治疗的头颈鳞状细胞癌具有预后意义。


DNA 拷贝数改变 (CNA) 在癌症中很常见，最近开发的 CNA 特征揭示了它们在分子肿瘤分层中对患者预后和卵巢癌铂耐药预测的价值。头颈鳞状细胞癌 (HNSCC) 的特征还在于高 CNA。在这项研究中，我们通过低覆盖率全基因组测序确定了来自荷兰多中心队列的 173 例人乳头瘤病毒阴性 HNSCC 的 CNA，并测试了七种癌症衍生的 CNA 特征对这些接受顺铂和放疗治疗的患者的预后价值。我们发现，在荷兰队列和癌症基因组图谱 HNSCC 数据集中，高 CNA 特征 1 (s1) 评分与所有其他特征的低值和更好的患者结果相关。高 s5 和 s7 分数与远处转移率增加相关，高 s6 分数与较差的总体生存率相关。高累积顺铂剂量可改善接受放化疗治疗的 HNSCC 患者的预后。在这里，我们发现 s1 高或 s6 低的肿瘤对顺铂剂量的变化最敏感。然而，高 s5 值会显着增加顺铂累积剂量低的患者的转移风险。总之，这表明导致这些 CNA 特征的过程影响 HNSCC 中的顺铂反应。总之，源自不同癌症类型的 CNA 特征具有预后意义，并且与 HNSCC 中的顺铂反应相关，表明它们代表了定义患者结果的潜在分子过程。