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| Verfasst von: | Tinhofer, Ingeborg [VerfasserIn]  |
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| | Budach, V. [VerfasserIn] |
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| | Saki, M. [VerfasserIn] |
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| | Konschak, R. [VerfasserIn] |
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| | Niehr, F. [VerfasserIn] |
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| | Jöhrens, K. [VerfasserIn] |
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| | Weichert, Wilko [VerfasserIn] |
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| | Linge, A. [VerfasserIn] |
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| | Lohaus, F. [VerfasserIn] |
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| | Krause, M. [VerfasserIn] |
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| | Neumann, K. [VerfasserIn] |
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| | Endris, Volker [VerfasserIn] |
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| | Sak, A. [VerfasserIn] |
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| | Stuschke, M. [VerfasserIn] |
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| | Balermpas, P. [VerfasserIn] |
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| | Rödel, C. [VerfasserIn] |
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| | Avlar, M. [VerfasserIn] |
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| | Grosu, A. L. [VerfasserIn] |
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| | Abdollahi, Amir [VerfasserIn] |
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| | Debus, Jürgen [VerfasserIn] |
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| | Belka, C. [VerfasserIn] |
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| | Pigorsch, S. [VerfasserIn] |
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| | Combs, S. E. [VerfasserIn] |
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| | Mönnich, D. [VerfasserIn] |
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| | Zips, D. [VerfasserIn] |
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| | Baumann, M. [VerfasserIn] |
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| Titel: | Targeted next-generation sequencing of locally advanced squamous cell carcinomas of the head and neck reveals druggable targets for improving adjuvant chemoradiation |
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| Verf.angabe: | I. Tinhofer, V. Budach, M. Saki, R. Konschak, F. Niehr, K. Jöhrens, W. Weichert, A. Linge, F. Lohaus, M. Krause, K. Neumann, V. Endris, A. Sak, M. Stuschke, P. Balermpas, C. Rödel, M. Avlar, A.L. Grosu, A. Abdollahi, J. Debus, C. Belka, S. Pigorsch, S.E. Combs, D. Mönnich, D. Zips, M. Baumann, for the DKTK-ROG |
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| E-Jahr: | 2016 |
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| Jahr: | 18 February 2016 |
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| Umfang: | 9 S. |
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| Fussnoten: | Gesehen am 11.02.2020 |
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| Titel Quelle: | Enthalten in: European journal of cancer |
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| Ort Quelle: | Amsterdam [u.a.] : Elsevier, 1992 |
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| Jahr Quelle: | 2016 |
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| Band/Heft Quelle: | 57(2016), Seite 78-86 |
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| ISSN Quelle: | 1879-0852 |
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| Abstract: | Background - Despite clear differences in clinical presentation and outcome, squamous cell carcinomas of the head and neck (SCCHN) arising from human papilloma virus (HPV) infection or heavy tobacco/alcohol consumption are treated equally. Next-generation sequencing is expected to reveal novel targets for more individualised treatment. - Patients and methods - Tumour specimens from 208 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity, all uniformly treated with adjuvant cisplatin-based chemoradiation, were included. A customised panel covering 211 exons from 45 genes frequently altered in SCCHN was used for detection of non-synonymous point and frameshift mutations. Mutations were correlated with HPV status and treatment outcome. - Results - Mutational profiles and HPV status were successfully established for 179 cases. HPV- tumours showed an increased frequency of alterations in tumour suppressor genes compared to HPV+ cases (TP53 67% versus 4%, CDKN2A 18% versus 0%). Conversely, HPV+ carcinomas were enriched for activating mutations in driver genes compared to HPV- cases (PIK3CA 30% versus 12%, KRAS 6% versus 1%, and NRAS 4% versus 0%). Hotspot TP53 missense mutations in HPV- carcinomas correlated with an increased risk of locoregional recurrence (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.5-12.1, P=0.006) and death (HR 2.2, 95% CI 1.1-4.4, P=0.021). In HPV+ SCCHN, driver gene mutations were associated per trend with a higher risk of death (HR 3.9, 95% CI 0.7-21.1, P=0.11). - Conclusions - Distinct mutation profiles in HPV- and HPV+ SCCHN identify subgroups with poor outcome after adjuvant chemoradiation. Mutant p53 and the phosphoinositide 3-kinase pathway were identified as potential druggable targets for subgroup-specific treatment optimisation. |
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| DOI: | doi:10.1016/j.ejca.2016.01.003 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.ejca.2016.01.003 |
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| | Volltext: http://www.sciencedirect.com/science/article/pii/S0959804916000393 |
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| | DOI: https://doi.org/10.1016/j.ejca.2016.01.003 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Adjuvant chemoradiation |
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| | Cisplatin |
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| | Head and neck cancer |
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| | Human papilloma virus |
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| | Mutation profiles |
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| K10plus-PPN: | 1689777338 |
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| Verknüpfungen: | → Zeitschrift |
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Targeted next-generation sequencing of locally advanced squamous cell carcinomas of the head and neck reveals druggable targets for improving adjuvant chemoradiation / Tinhofer, Ingeborg [VerfasserIn]; 18 February 2016 (Online-Ressource)
