Oncogenic driver mutations predict outcome in a cohort of head and neck squamous cell carcinoma (HNSCC) patients within a clinical trial.

Clinical Trials as Topic Cohort Studies Female High-Throughput Nucleotide Sequencing / methods Humans Male Middle Aged Mutation Papillomavirus Infections Phosphatidylinositol 3-Kinases / metabolism Prognosis Signal Transduction Squamous Cell Carcinoma of Head and Neck / genetics Survival Rate

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
06 10 2020
Historique:
received: 05 04 2020
accepted: 13 08 2020
entrez: 7 10 2020
pubmed: 8 10 2020
medline: 9 3 2021
Statut: epublish

Résumé

234 diagnostic formalin-fixed paraffin-embedded (FFPE) blocks from homogeneously treated patients with locally advanced head and neck squamous cell carcinoma (HNSCC) within a multicentre phase III clinical trial were characterised. The mutational spectrum was examined by next generation sequencing in the 26 most frequent oncogenic drivers in cancer and correlated with treatment response and survival. Human papillomavirus (HPV) status was measured by p16INK4a immunohistochemistry in oropharyngeal tumours. Clinicopathological features and response to treatment were measured and compared with the sequencing results. The results indicated TP53 as the most mutated gene in locally advanced HNSCC. HPV-positive oropharyngeal tumours were less mutated than HPV-negative tumours in TP53 (p < 0.01). Mutational and HPV status influences patient survival, being mutated or HPV-negative tumours associated with poor overall survival (p < 0.05). No association was found between mutations and clinicopathological features. This study confirmed and expanded previously published genomic characterization data in HNSCC. Survival analysis showed that non-mutated HNSCC tumours associated with better prognosis and lack of mutations can be identified as an important biomarker in HNSCC. Frequent alterations in PI3K pathway in HPV-positive HNSCC could define a promising pathway for pharmacological intervention in this group of tumours.

Identifiants

DOI: 10.1038/s41598-020-72927-2 PMID: 33024167 PMC: PMC7539152
pubmed: 33024167
doi: 10.1038/s41598-020-72927-2
pii: 10.1038/s41598-020-72927-2
pmc: PMC7539152
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

16634

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Auteurs

Javier Fernández-Mateos (J)

Medical Oncology Service, University Hospital of Salamanca-IBSAL, 37007, Salamanca, Spain.
Biomedical Research Institute of Salamanca (IBSAL), SACYL-University of Salamanca-CSIC, 37007, Salamanca, Spain.
Molecular Medicine Unit-IBSAL, Department of Medicine, University of Salamanca, 37007, Salamanca, Spain.
Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-CSIC, 37007, Salamanca, Spain.

Jéssica Pérez-García (J)

Molecular Medicine Unit-IBSAL, Department of Medicine, University of Salamanca, 37007, Salamanca, Spain.
Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-CSIC, 37007, Salamanca, Spain.

Raquel Seijas-Tamayo (R)

Medical Oncology Service, University Hospital of Salamanca-IBSAL, 37007, Salamanca, Spain.
Biomedical Research Institute of Salamanca (IBSAL), SACYL-University of Salamanca-CSIC, 37007, Salamanca, Spain.

Ricard Mesía (R)

Medical Oncology Department, Institut Català d'Oncologia, L'Hospitalet de Llobregat, Universitat de Barcelona, IDIBELL, 08908, Barcelona, Spain.

Jordi Rubió-Casadevall (J)

Medical Oncology Service, Institut Català d'Oncologia, 17007, Gerona, Spain.

Carlos García-Girón (C)

Medical Oncology Service, Hospital Universitario de Burgos, 09006, Burgos, Spain.

Lara Iglesias (L)

Medical Oncology Service, Hospital Universitario 12 de Octubre, 28041, Madrid, Spain.

Alberto Carral Maseda (A)

Medical Oncology Service, Hospital Universitario Lucus Augusti, 27003, Lugo, Spain.

Juan Carlos Adansa Klain (JC)

Medical Oncology Service, University Hospital of Salamanca-IBSAL, 37007, Salamanca, Spain.
Biomedical Research Institute of Salamanca (IBSAL), SACYL-University of Salamanca-CSIC, 37007, Salamanca, Spain.

Miren Taberna (M)

Medical Oncology Department, Institut Català d'Oncologia, L'Hospitalet de Llobregat, Universitat de Barcelona, IDIBELL, 08908, Barcelona, Spain.

Silvia Vazquez (S)

Medical Oncology Department, Institut Català d'Oncologia, L'Hospitalet de Llobregat, Universitat de Barcelona, IDIBELL, 08908, Barcelona, Spain.

María Asunción Gómez (MA)

Pathologist Service, University Hospital of Salamanca, 37007, Salamanca, Spain.

Edel Del Barco (E)

Medical Oncology Service, University Hospital of Salamanca-IBSAL, 37007, Salamanca, Spain.
Biomedical Research Institute of Salamanca (IBSAL), SACYL-University of Salamanca-CSIC, 37007, Salamanca, Spain.

Alberto Ocana (A)

Hospital Clínico San Carlos, IdISSC, CIBERONC, 28040, Madrid, Spain.
Centro Regional de Investigaciones Biomédicas, Universidad de Castilla La Mancha, 13071, Albacete, Spain.

Rogelio González-Sarmiento (R)

Biomedical Research Institute of Salamanca (IBSAL), SACYL-University of Salamanca-CSIC, 37007, Salamanca, Spain. gonzalez@usal.es.
Molecular Medicine Unit-IBSAL, Department of Medicine, University of Salamanca, 37007, Salamanca, Spain. gonzalez@usal.es.
Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-CSIC, 37007, Salamanca, Spain. gonzalez@usal.es.

Juan Jesús Cruz-Hernández (JJ)

Medical Oncology Service, University Hospital of Salamanca-IBSAL, 37007, Salamanca, Spain. jjcruz@usal.es.
Biomedical Research Institute of Salamanca (IBSAL), SACYL-University of Salamanca-CSIC, 37007, Salamanca, Spain. jjcruz@usal.es.
Molecular Medicine Unit-IBSAL, Department of Medicine, University of Salamanca, 37007, Salamanca, Spain. jjcruz@usal.es.
Institute of Molecular and Cellular Biology of Cancer (IBMCC), University of Salamanca-CSIC, 37007, Salamanca, Spain. jjcruz@usal.es.

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