1. Targeted sequencing reveals TP53 as a potential diagnostic biomarker in the post-treatment surveillance of head and neck cancer.
- Author
-
van Ginkel JH, de Leng WW, de Bree R, van Es RJ, and Willems SM
- Subjects
- Aged, Aged, 80 and over, Bone Neoplasms genetics, Bone Neoplasms secondary, Carcinoma, Squamous Cell blood, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell surgery, Circulating Tumor DNA blood, Class I Phosphatidylinositol 3-Kinases genetics, Cyclin-Dependent Kinase 4 genetics, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p18 genetics, DNA Mutational Analysis methods, F-Box-WD Repeat-Containing Protein 7 genetics, Female, Head and Neck Neoplasms blood, Head and Neck Neoplasms pathology, Head and Neck Neoplasms surgery, High-Throughput Nucleotide Sequencing methods, Humans, Liquid Biopsy, Liver Neoplasms genetics, Liver Neoplasms secondary, Lung Neoplasms genetics, Lung Neoplasms secondary, Lymphatic Metastasis, Male, Middle Aged, Mutation, Proto-Oncogene Proteins p21(ras) genetics, Retinoblastoma Binding Proteins genetics, Retrospective Studies, Skin Neoplasms genetics, Skin Neoplasms secondary, Squamous Cell Carcinoma of Head and Neck, Tumor Burden genetics, Ubiquitin-Protein Ligases genetics, Biomarkers, Tumor genetics, Carcinoma, Squamous Cell genetics, Circulating Tumor DNA genetics, Head and Neck Neoplasms genetics, Neoplasm Recurrence, Local genetics, Tumor Suppressor Protein p53 genetics
- 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., Competing Interests: The authors declare no conflicts of interest.
- Published
- 2016
- Full Text
- View/download PDF