<b><i>TP53</i></b> Y220C Is a Hotspot Mutation in Oropharyngeal Squamous Cell Carcinoma

Abstract

Objectives: Although TP53 mutations in head and neck squamous cell carcinoma (HNSCC) have been extensively studied, their association with the different subsites in the head and neck region has never been described. Methods: Sanger sequence analysis evaluating exons 4-9 in the TP53 gene was performed on 116 HNSCC patients. The exon location, exact codon and corresponding substitution in relation to the anatomical site (subsite) of the HNSCC were evaluated. Results: We found nonsynonymous TP53 mutations in 70% (81/116) of the patients. In oral cavity carcinomas, most mutations occurred in exon 7 (37%). In oropharyngeal and laryngeal tumors, mutations were mainly found in exons 6 and 7. The most common mutation was located in codon 220, and all of these were an Y220C mutation. Five out of nine (56%) Y220C mutations occurred in oropharyngeal tumors. Additionally, 22% of all mutations observed in oropharyngeal squamous cell carcinoma (OPSCC) consisted of Y220C mutations. Conclusion: In this study, the subsite-related distribution of TP53 mutations underlines the biological diversity between tumors arising from different anatomical regions in the head and neck region. Moreover, the Y220C mutation was by far the most prevalent TP53 mutation in HNSCC and a relative hotspot mutation in the oropharynx.

NAMPT Inhibitor and P73 Activator Represses P53 R175H Mutated HNSCC Cell Proliferation in a Synergistic Manner

“…To the best of our knowledge, only two articles have reported head and neck cancer; p53 mutant aggregation was reported in the HNSCC cell line Detroit 562 with a p53 R175H mutation [25,37]. There are several hotspot mutations in codons 175,179,196,213,220,245,248,273 and 282 of p53 in HNSCC [38,39], and HNSCC can be divided into different subtypes [40,41]. More information about whether p53 hotspot mutations can become aggregated or not in HNSCC, and how aggregated mutant p53 obtains GoF function in different sub-types of HNSCC, will need to be further addressed in the future.…”

“…To the best of our knowledge, only two articles have reported head and neck cancer; p53 mutant aggregation was reported in the HNSCC cell line Detroit 562 with a p53 R175H mutation [25,37]. There are several hotspot mutations in codons 175, 179, 196, 213, 220, 245, 248, 273 and 282 of p53 in HNSCC [38,39], and HNSCC can be divided into different subtypes…”

Targeted sequencing reveals TP53 as a potential diagnostic biomarker in the post-treatment surveillance of head and neck cancer

“…Demographic and clinical data, including history of tobacco and alcohol use, were retrieved from hospital charts. Smoking and alcohol consumption habits were classified as previously described [ 58 ].…”

“…primary tumor, metastasis or recurrence) was mainly based on TP53 clonality. If a clonal relationship could not be ruled out, we based subtype determination on clinical suspicion and date of incidence as described previously [ 58 ]. In the same manner, distinction was made between second primary tumors, metastases and recurrences.…”