title: Targeted sequencing reveals TP53 as a potential diagnostic biomarker in the post-treatment surveillance of head and neck cancer.
abstract: Head and neck squamous cell carcinomas (HNSCC) form a large heterogeneous group of tumors and have a relatively poor outcome in advanced cases. Revealing the underlying genetic mutations in HNSCC facilitates the development of diagnostic biomarkers, which might lead to improved diagnosis and post treatment surveillance. We retrospectively analyzed mutational hotspots using targeted next-generation sequencing (NGS) of 239 HNSCC tumor samples in order to examine the mutational profile of HNSCC. Furthermore, we assessed prevalence, co-occurrence, and synonymy of gene mutations in (matched) tumor samples. TP53 was found mutated the most frequent with mutation rates of up to 83% in all tumors, compared to mutation rates of between 0 and 21% of CDKN2A, PIK3CA, HRAS, CDK4, FBXW7 and RB1. Mutational co-occurrence predominantly existed between TP53 and PIK3CA, TP53 and CDKN2A, and HRAS and PIK3CA. Mutational synonymy between primary tumor and associated metastasis and recurrence was present in respectively 88% and 89%. TP53 mutations were concordantly mutated in 95% of metastases and in 91% of recurrences. This indicates TP53 mutations to be highly prevalent and concordant in primary tumors and associated locoregional metastases and recurrences. In turn, this provides ground for further investigating the use of TP53 mutations as diagnostic biomarkers in HNSCC patients.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Joost H
authors.initials: JH
authors.lastname: van Ginkel
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Wendy W J
authors.initials: WW
authors.lastname: de Leng
authors.affiliation: Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Remco
authors.initials: R
authors.lastname: de Bree
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Robert J J
authors.initials: RJ
authors.lastname: van Es
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Willems
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001859:Bone Neoplasms / Q000235:genetics / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000074141:Circulating Tumor DNA / Q000097:blood / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D000073979:F-Box-WD Repeat-Containing Protein 7 / Q000235:genetics; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D000073890:Liquid Biopsy; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D056286:Retinoblastoma Binding Proteins / Q000235:genetics; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000235:genetics / Q000556:secondary; D000077195:Squamous Cell Carcinoma of Head and Neck; D047368:Tumor Burden / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D000074141:Circulating Tumor DNA; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C000606393:RB1 protein, human; D056286:Retinoblastoma Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: TP53; diagnostic biomarkers; head and neck cancer; mutations; next-generation sequencing