Ovarian cancer-derived copy number alterations signatures are prognostic in chemoradiotherapy-treated head and neck squamous cell carcinoma

Paul B.M. Essers, Martijn van der Heijden, David Vossen, Reinout H. de Roest, C. René Leemans, Ruud H. Brakenhoff, Michiel W.M. van den Brekel, Harry Bartelink, Marcel Verheij, Conchita Vens

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1732-1739
Number of pages8
JournalInternational Journal of Cancer
Volume147
Issue number6
DOIs
Publication statusPublished - 15 Sep 2020

Bibliographical note

Funding Information:
We would like to thank the NKI Genomics Core Facility for performing RNA sequencing, the NKI RHPC facility for providing computational resources, and the Core Facility-Molecular Pathology and Biobank (CFMPB) for collecting and preparing tissue samples. This research was funded by the EU 7th framework program (257144 ARTFORCE), the Dutch Cancer Society (KWF-A6C7072) and the Brunel and Verwelius funds.

Funding Information:
We would like to thank the NKI Genomics Core Facility for performing RNA sequencing, the NKI RHPC facility for providing computational resources, and the Core Facility‐Molecular Pathology and Biobank (CFMPB) for collecting and preparing tissue samples. This research was funded by the EU 7th framework program (257144 ARTFORCE), the Dutch Cancer Society (KWF‐A6C7072) and the Brunel and Verwelius funds.

Publisher Copyright:
© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC

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