Absence of disruptive TP53 mutations in high-risk human papillomavirus-driven neck squamous cell carcinoma of unknown primary
Por:
Boscolo-Rizzo, P, Schroeder, L, Sacchetto, V, Holzinger, D, Da Mosto, MC, Tirelli, G, Dal Cin, E, Mantovani, M, Menegaldo, A, Del Mistro, A, Romeo, S, Dei Tos, AP, Niero, M, Rigo, S, Dyckhoff, G, Hess, J, Alemany, L, Quer, M, Leon, X, Polesel, J, Pawlita, M, Bertorelle, R
Publicada:
1 nov 2019
Ahead of Print:
1 ago 2019
Resumen:
Background To enforce the evidence for causality between high-risk human papillomavirus (hrHPV) infections and neck squamous cell carcinoma from unknown primary (NSCCUP) and provide biological basis for treatment de-intensification, we searched for TP53 mutations in association with HPV status. Methods TP53 mutations were searched for by amplification of exons 4 to 10. Results Of the 70 NSCCUP, 27 (39%) harbored HPV infection. TP53 sequencing resulted in the identification of 19 patients harboring single mutations including 16 disruptive alterations (84%). The association of TP53 mutations and HPV could be evaluated in 48 NSCCUP including those with disruptive mutation in any exon (n = 16) and those without mutations but with complete sequence of exons 4 to 9 (n = 32): no disruptive mutations were found in the 17 HPV-driven NSCCUP but in 16 of the 31 non-HPV-driven NSCCUP (P = .0002). Conclusion In a fraction of cases, NSCCUP is an HPV-driven entity harboring wild-type TP53 gene or nondisruptive TP53 mutations. HPV-driven NSCCUP might benefit from treatment de-intensification.
Filiaciones:
Boscolo-Rizzo, P:
Univ Padua, Reg Ctr Head & Neck Canc, Dept Neurosci, Azienda ULSS Marca Trevigiana 2, Ple Osped 1, I-31100 Treviso, Italy
Schroeder, L:
German Canc Res Ctr, Mol Diagnost Oncogen Infect Infect Inflammat & Ca, Heidelberg, Germany
Sacchetto, V:
Veneto Inst Oncol IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy
Holzinger, D:
German Canc Res Ctr, Mol Diagnost Oncogen Infect Infect Inflammat & Ca, Heidelberg, Germany
Da Mosto, MC:
Univ Padua, Reg Ctr Head & Neck Canc, Dept Neurosci, Azienda ULSS Marca Trevigiana 2, Ple Osped 1, I-31100 Treviso, Italy
Tirelli, G:
Azienda Sanitaria Univ Integrata Trieste ASUITS, Dept Otorhinolaryngol & Head & Neck Surg, Trieste, Italy
Dal Cin, E:
Azienda Sanitaria Univ Integrata Trieste ASUITS, Dept Otorhinolaryngol & Head & Neck Surg, Trieste, Italy
Mantovani, M:
Univ Padua, Reg Ctr Head & Neck Canc, Dept Neurosci, Azienda ULSS Marca Trevigiana 2, Ple Osped 1, I-31100 Treviso, Italy
Menegaldo, A:
Univ Padua, Reg Ctr Head & Neck Canc, Dept Neurosci, Azienda ULSS Marca Trevigiana 2, Ple Osped 1, I-31100 Treviso, Italy
Del Mistro, A:
Veneto Inst Oncol IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy
Romeo, S:
San Dona Piave Hosp, Azienda ULSS Veneto Orientale 4, Dept Pathol, San Dona Di Piave, Italy
Dei Tos, AP:
Univ Padua, Azienda ULSS Marca Trevigiana 2, Dept Pathol, Treviso, Italy
Niero, M:
Univ Padua, Azienda ULSS Marca Trevigiana 2, Dept Pathol, Treviso, Italy
Rigo, S:
Azienda Sanitaria Univ Integrata Trieste ASUITS, Dept Otorhinolaryngol & Head & Neck Surg, Trieste, Italy
Dyckhoff, G:
Univ Hosp Heidelberg, Dept Otorhinolaryngol Head & Neck Surg, Mol Cell Biol Grp, Heidelberg, Germany
Hess, J:
Univ Hosp Heidelberg, Dept Otorhinolaryngol Head & Neck Surg, Sect Expt & Translat Head & Neck Oncol, Heidelberg, Germany
German Canc Res Ctr, Mol Mech Head & Neck Tumors, Heidelberg, Germany
Alemany, L:
IDIBELL, ICO, Unit Infect & Canc, Barcelona, Spain
CIBERESP, Madrid, Spain
Quer, M:
Hosp Santa Creu & Sant Pau, Serv Otorrinolaringol, Carrer St Quinti, Barcelona, Spain
Leon, X:
Hosp Santa Creu & Sant Pau, Serv Otorrinolaringol, Carrer St Quinti, Barcelona, Spain
Polesel, J:
Ctr Riferimento Oncol Aviano CRO IRCCS, Unit Canc Epidemiol, Aviano, Italy
Pawlita, M:
German Canc Res Ctr, Mol Diagnost Oncogen Infect Infect Inflammat & Ca, Heidelberg, Germany
Bertorelle, R:
Veneto Inst Oncol IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy
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