Universität zu Köln

Reder, Henrike, Wagner, Steffen ORCID: 0000-0003-0873-1601, Wuerdemann, Nora, Langer, Christine, Sandmann, Sarah ORCID: 0000-0002-5011-0641, Braeuninger, Andreas, Dugas, Martin, Gattenloehner, Stefan, Wittekindt, Claus and Klussmann, Jens Peter ORCID: 0000-0002-8223-7954 (2021). Mutation patterns in recurrent and/or metastatic oropharyngeal squamous cell carcinomas in relation to human papillomavirus status. Cancer Med., 10 (4). S. 1347 - 1357. HOBOKEN: WILEY. ISSN 2045-7634

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Reder, Henrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagner, Steffen UNSPECIFIED orcid.org/0000-0003-0873-1601 UNSPECIFIED Wuerdemann, Nora UNSPECIFIED UNSPECIFIED UNSPECIFIED Langer, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED Sandmann, Sarah UNSPECIFIED orcid.org/0000-0002-5011-0641 UNSPECIFIED Braeuninger, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Dugas, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Gattenloehner, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Wittekindt, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Klussmann, Jens Peter UNSPECIFIED orcid.org/0000-0002-8223-7954 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-580158
DOI:	10.1002/cam4.3741
Journal or Publication Title:	Cancer Med.
Volume:	10
Number:	4
Page Range:	S. 1347 - 1357
Date:	2021
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	2045-7634
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58015