Analysis of genetic variants of frequently mutated genes in human papillomavirus-negative primary head and neck squamous cell carcinoma, resection margins, local recurrences and corresponding circulating cell-free DNA.
HNSCC
cell-free DNA
liquid biopsy
next-generation sequencing
resection margins
Journal
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
ISSN: 1600-0714
Titre abrégé: J Oral Pathol Med
Pays: Denmark
ID NLM: 8911934
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
received:
19
06
2022
accepted:
22
06
2022
pubmed:
28
7
2022
medline:
14
9
2022
entrez:
27
7
2022
Statut:
ppublish
Résumé
Head and neck squamous cell carcinoma remains a substantial burden to global health. Despite evolving therapies, 5-year survival is <50% and unlike in other cancers, reliable molecular biomarkers to guide treatment do not exist. We performed targeted panel next-generation sequencing to analyse somatic variants from primary and recurrent tumour tissue, corresponding resection margins and cell-free DNA from intra-operatively collected plasma samples from eight patients with human papillomavirus-negative head and neck squamous cell carcinoma. Patients were primarily treated with curative-intent surgery and received subsequent adjuvant treatment. The most frequently mutated gene was TP53. Other mutated genes included NOTCH1, NF1 and CDKN2A among others. A total of 20.8% of variants were shared between primary tumour and resection margin. Out of all the variants detected, 37.5% were shared between cell-free DNA and primary tumour, whereas 12.5% were commonly found in cell-free DNA, primary tumour and resection margin. Mutational profiling was able to distinguish between a locoregional recurrence and a second primary tumour by identifying a different TP53 mutation in the primary tumour compared to the recurrent tumour in addition to private FBXW7 and CTNNB1 mutations. We also identified identical TP53 and PIK3CA mutations in another primary tumour and corresponding recurrence. Molecular profiling of cell-free DNA and resection margins has potential applications in clinical practice to guide future treatment decisions.
Sections du résumé
BACKGROUND
BACKGROUND
Head and neck squamous cell carcinoma remains a substantial burden to global health. Despite evolving therapies, 5-year survival is <50% and unlike in other cancers, reliable molecular biomarkers to guide treatment do not exist.
METHODS
METHODS
We performed targeted panel next-generation sequencing to analyse somatic variants from primary and recurrent tumour tissue, corresponding resection margins and cell-free DNA from intra-operatively collected plasma samples from eight patients with human papillomavirus-negative head and neck squamous cell carcinoma. Patients were primarily treated with curative-intent surgery and received subsequent adjuvant treatment.
RESULTS
RESULTS
The most frequently mutated gene was TP53. Other mutated genes included NOTCH1, NF1 and CDKN2A among others. A total of 20.8% of variants were shared between primary tumour and resection margin. Out of all the variants detected, 37.5% were shared between cell-free DNA and primary tumour, whereas 12.5% were commonly found in cell-free DNA, primary tumour and resection margin. Mutational profiling was able to distinguish between a locoregional recurrence and a second primary tumour by identifying a different TP53 mutation in the primary tumour compared to the recurrent tumour in addition to private FBXW7 and CTNNB1 mutations. We also identified identical TP53 and PIK3CA mutations in another primary tumour and corresponding recurrence.
CONCLUSION
CONCLUSIONS
Molecular profiling of cell-free DNA and resection margins has potential applications in clinical practice to guide future treatment decisions.
Substances chimiques
Cell-Free Nucleic Acids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
738-746Subventions
Organisme : Munich Clinician Scientist Programme
Organisme : Verein zur Förderung von Wissenschaft und Forschung an der Medizinischen Fakultät der LMU München e.V.
Informations de copyright
© 2022 The Authors. Journal of Oral Pathology & Medicine published by John Wiley & Sons Ltd.
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