CC BY-NC-ND 4.0 · Laryngorhinootologie 2018; 97(S 02): S124
DOI: 10.1055/s-0038-1640139
Abstracts
Onkologie: Oncology

Detection of Tumor-Specific Genetic Aberrations in Liquid Biopsies of Patients with HPV-associated Oropharyngeal Squamous Cell Carcinoma

H Reder
1   HNO-Heilkunde, Kopf-Halschirurgie, Gießen
,
N Würdemann
1   HNO-Heilkunde, Kopf-Halschirurgie, Gießen
,
U Gamerdinger
2   Institut für Pathologie, Gießen
,
S Sandmann
3   Institut für Medizinische Informatik, Münster
,
A Bräuninger
2   Institut für Pathologie, Gießen
,
S Wagner
1   HNO-Heilkunde, Kopf-Halschirurgie, Gießen
,
C Wittekindt
1   HNO-Heilkunde, Kopf-Halschirurgie, Gießen
,
M Dugas
3   Institut für Medizinische Informatik, Münster
,
S Gattenlöhner
2   Institut für Pathologie, Gießen
,
JP Klußmann
1   HNO-Heilkunde, Kopf-Halschirurgie, Gießen
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    Introduction:

    In addition to tobacco and alcohol, infection with HPV is recognized as major risk factor for the development of oropharyngeal squamous cell carcinoma (OPSCC). Although HPV-associated OPSCC have a more favorable prognosis and differ in their clinical and biological characteristics from HPV-negative OPSCC, both entities are treated equally. The aim of the project is the identification and detection of genetic aberrations associated with an unfavorable course of disease in HPV-positive OPSCC.

    Methods:

    An HPV-specific panel for targeted next generation sequencing (tNGS) was designed (covering regions of 24 genes). DNA from HPV-associated primary tumors (n = 26) and sequential plasma samples was sequenced. HPV-DNA in cell-free DNA (cfDNA) was analyzed by qPCR. Chromosomal aberrations were determined with a SNP-array.

    Results:

    Tumor-specific mutations and HPV-DNA can be detected pre-therapeutically in cfDNA; posttherapeutically, its amount decreases correlating to treatment strategies. With our limited tNGS HPV panel, patients with an unfavorable course of disease accumulate around 2.4-times more mutations compared to patients with a favorable course. So far, chromosomal aberrations have been analyzed in patients with a severe course of disease. Some regions (e.g. loss of CYLD on chromosome 16q12) are altered in several samples.

    Conclusions:

    Patients with HPV-associated OPSCC and an unfavorable course of disease have more genetic aberrations than those with a favorable course. The impact of these mutations and aberrations will be further analyzed bioinformatically. HPV-DNA and tumor-specific mutations could be detected in cfDNA pre-, but not post-therapeutically.


    #

    No conflict of interest has been declared by the author(s).

    M.Sc. Henrike Reder
    HNO-Heilkunde, Kopf-Halschirurgie,
    Klinikstraße 33, 35392,
    Gießen

    Publication History

    Publication Date:
    18 April 2018 (online)

    © 2018. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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