Universität zu Köln

Reder, Henrike ORCID: 0000-0001-5844-223X, Wagner, Steffen, Gamerdinger, Ulrike, Sandmann, Sarah ORCID: 0000-0002-5011-0641, Wuerdemann, Nora, Braeuninger, Andreas, Dugas, Martin, Gattenloehner, Stefan, Klussmann, Jens Peter and Wittekindt, Claus (2019). Genetic alterations in human papillomavirus-associated oropharyngeal squamous cell carcinoma of patients with treatment failure. Oral Oncol., 93. S. 59 - 66. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1879-0593

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Abstract

Objectives: Despite improved survival rates of patients with HPV-associated OPSCC, a subset has distant metastasis or develops local recurrence during follow-up. To investigate potential underlying genetic alterations, we analyzed patients with HPV-driven OPSCC who suffered from recurrence in comparison to matching pairs with successful tumor control. Materials and methods: We performed chromosomal copy number analyses and targeted next generation sequencing using a custom panel comprising genes that are frequently mutated in HPV-associated OPSCC. Results: Specific differences regarding chromosomal aberrations were not observed between both groups. In HPV-driven OPSCC from patients with recurrence we found higher mutation rates compared to patients with successful tumor control. Especially mutation rates of HRAS (p <= 0.05) PIK3R1, STK11 and TP63 (p <= 0.1 each) were statistically significant or trending towards significance. The respective genes can be linked to transcription factors and signaling pathways involved in cell cycle regulation, proliferation and survival. Additionally, combinations of alterations were observed on chromosomes 16 and 19, which might also influence outcome. Conclusion: Patients with HPV-driven OPSCC who develop recurrence or have metastasis may be defined by genetic alterations that might be responsible for poor outcome after standard therapy. This might be of importance for stratification in future de-escalation and targeted therapy.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Reder, Henrike UNSPECIFIED orcid.org/0000-0001-5844-223X UNSPECIFIED Wagner, Steffen UNSPECIFIED UNSPECIFIED UNSPECIFIED Gamerdinger, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Sandmann, Sarah UNSPECIFIED orcid.org/0000-0002-5011-0641 UNSPECIFIED Wuerdemann, Nora UNSPECIFIED UNSPECIFIED UNSPECIFIED Braeuninger, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Dugas, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Gattenloehner, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Klussmann, Jens Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Wittekindt, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-147411
DOI:	10.1016/j.oraloncology.2019.04.013
Journal or Publication Title:	Oral Oncol.
Volume:	93
Page Range:	S. 59 - 66
Date:	2019
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	1879-0593
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COPY NUMBER ALTERATIONS; NECK-CANCER; H-RAS; GENOMIC CHARACTERIZATION; FUNCTIONAL-ANALYSIS; DE-ESCALATION; K-RAS; N-RAS; HEAD; HPV Multiple languages Oncology; Dentistry, Oral Surgery & Medicine Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14741