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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

The TP53 Codon 72 Arginine Polymorphism Is Found with Increased TP53 Somatic Mutations in HPV(-) and in an Increased

Svein Erik Moe¹, Fredrik A Erland¹, Siren Fromreide²

¹Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital (HUS), N-5020 Bergen, Norway.

|July 29, 2023

Abstract

Background:

Somatic TP53 mutations are frequent in head and neck squamous cell carcinoma (HNSCC) and are important pathogenic factors.

Objective:

To study TP53 mutations relative to the presence of human papillomavirus (HPV) in tumors in HNSCC patients.

Methods:

Using a custom-made next-generation sequencing (NGS) panel on formalin-fixed, paraffin-embedded tumor tissue, we analyzed somatic TP53 mutations and the TP53 single-nucleotide polymorphism (SNP) codon 72 (P72R; rs1042522) (proline → arginine) from 104 patients with HNSCC.

Results:

Only 2 of 44 patients with HPV-positive (HPV(+)) HNSCC had a TP53 somatic mutation, as opposed to 42/60 HPV-negative (HPV(-)) HNSCC patients (p < 0.001). Forty-five different TP53 somatic mutations were detected. Furthermore, in HPV(-) patients, we determined an 80% prevalence of somatic TP53 mutations in the TP53 R72 polymorphism cohort versus 40% in the TP53 P72 cohort (p = 0.001). A higher percentage of patients with oral cavity SCC had TP53 mutations than HPV(-) oropharyngeal (OP) SCC patients (p = 0.012). Furthermore, 39/44 HPV(+) tumor patients harbored the TP53 R72 polymorphism in contrast to 42/60 patients in the HPV(-) group (p = 0.024).

Conclusions:

Our observations show that TP53 R72 polymorphism is associated with a tumor being HPV(+). We also report a higher percentage of somatic TP53 mutations with R72 than P72 in HPV(-) HNSCC patients.

Keywords:

HPV TP53 head and neck cancer singe-nucleotide polymorphism somatic mutation

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