Journalartikel

Mutation patterns in recurrent and/or metastatic oropharyngeal squamous cell carcinomas in relation to human papillomavirus status


AutorenlisteReder, Henrike; Wagner, Steffen; Wuerdemann, Nora; Langer, Christine; Sandmann, Sarah; Braeuninger, Andreas; Dugas, Martin; Gattenloehner, Stefan; Wittekindt, Claus; Klussmann, Jens Peter

Jahr der Veröffentlichung2021

Seiten1347-1356

ZeitschriftCancer Medicine

Bandnummer10

Heftnummer4

ISSN2045-7634

Open Access StatusGold

DOI Linkhttps://doi.org/10.1002/cam4.3741

VerlagWiley


Abstract
Patients with HPV-driven (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) have a significantly improved overall survival compared to patients with HPV-negative (HPV-) OPSCC. Nevertheless, 13%-25% of patients with HPV+OPSCC develop local/distant recurrence (LDR) and have a course of disease similar to HPV-OPSCC. We hypothesize that HPV+OPSCCs of patients with LDR have a mutation frequency and pattern similar to HPV-OPSCCs, which is associated with severe outcome. We performed targeted next-generation sequencing using a customized gene panel and compared data from 56 matched HPV+and HPV-OPSCC of patients with/without LDR regarding protein-altering variants. Despite improved overall survival of patients with HPV+OPSCC, those who develop LDR show a strongly reduced survival rate that is similar or even worse compared to HPV-OPSCC patients. Overall, the number of mutations was similar in OPSCC of patients with and without LDR. In total and with respect to TP53, HPV-OPSCC had significantly more protein-altering mutations than HPV+OPSCC. The number of mutations was similar in HPV-OPSCC of patients with and without LDR with the exception of FAT1, which was mutated more frequently in patients without LDR. In HPV+OPSCC, HRAS, PIK3R1, STK11 and TP63 were more frequently mutated in patients with LDR compared to patients without. HPV+OPSCC of patients with LDR have a similar mutation pattern as HPV-OPSCC, except TP53, which was mutated to a significantly lower extent. In conclusion, HPV-and HPV+OPSCC with LDR have similar mutation counts in the analyzed genes. We suspect that the number of mutations is not causal for disease progression, rather specific mutations could be important.



Zitierstile

Harvard-ZitierstilReder, H., Wagner, S., Wuerdemann, N., Langer, C., Sandmann, S., Braeuninger, A., et al. (2021) Mutation patterns in recurrent and/or metastatic oropharyngeal squamous cell carcinomas in relation to human papillomavirus status, Cancer Medicine, 10(4), pp. 1347-1356. https://doi.org/10.1002/cam4.3741

APA-ZitierstilReder, H., Wagner, S., Wuerdemann, N., Langer, C., Sandmann, S., Braeuninger, A., Dugas, M., Gattenloehner, S., Wittekindt, C., & Klussmann, J. (2021). Mutation patterns in recurrent and/or metastatic oropharyngeal squamous cell carcinomas in relation to human papillomavirus status. Cancer Medicine. 10(4), 1347-1356. https://doi.org/10.1002/cam4.3741



Schlagwörter


Human papillomavirusOROPHARYNGEAL CANCERp53 geneRECURRENCEsquamous cell carcinoma


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