Novel p53 codon 240 Ser > Thr coding region mutation in the patients of oral squamous cell carcinoma (OSCC)

Abstract

Chewing habits of tobacco, betel quid (paan), and betel nut (chhaliya) are common traditions in Pakistan. Different other preparations and combination of flavors with tobacco, paan, and chhaliya ingredients are commonly available in the market and have received considerable attention as sources of carcinogens that promote OSCC. Mutagens can damage DNA and generate promutagenic lesions. The germ line mutation/polymorphism of p53 gene has been reported to be involved in multiple steps of carcinogenesis. This study aims to find out the loss of TP53 functions due to mutation/polymorphism caused by genomic alteration and interaction with tobacco-related ingredients.Tissue and blood specimens from 260 OSCC patients were collected and compared with blood samples of 260 age- and sex-matched controls. Mutations in exons 2-11 of p53 gene were examined by PCR-SSCP and directly sequenced.A novel mutation was found in exon 7 of p53 gene. This mutation was observed in the tumors of the OSCC patients. The blood samples of the patients and the controls did not show the nucleotide change in this region. The "AGT" to "ACT" missense mutation was identified at position 719 at TP53. This results in the substitution of amino acid serine with threonine at codon 240 of p53 protein.This novel missence mutation in the DNA-binding domain indicated that the DNA structure may be damaged by the use of exogenous DNA-damaging agents, including tobacco-related carcinogens present in gutka, niswar, and manpuri, which may result in the loss of p53 protein function.

Major apoptotic mechanisms and genes involved in apoptosis

“…Recently, Saleem et al analyzed loss of function mutations in p53 gene in the patients of oral squamous cell carcinoma and found that AGT to ACT missense mutation in DNA binding domain may result in impaired p53 function. In chronic lymphocytic leukemia patients, missense mutations in DNA binding motif were correlated with poor survival [154,155]. p53 has been considered as a significant player of apoptosis in many studies, and there is a growing accumulation of articles revealing its role in many malignancies.…”

Genetic profile of PTEN gene in Indian oral squamous cell carcinoma primary tumors

“…The oxidative stress and subsequent ROS generation leads to cell proliferation, ended into tumorigenesis depending upon the degree of ROS production. A continual exposure to such carcinogens can result in lesions in the oral cavity and consequently end into cancer .…”

Mutant p53 in head and neck squamous cell carcinoma: Molecular mechanism of gain‑of‑function and targeting therapy (Review)

“…1A ). In addition, a new mutation in exon 7 of the p53 gene has been identified in the tumors of patients with oral squamous cell carcinoma (OSCC) ( 15 ). A missense mutation resulting in a codon alteration from ‘AGT’ to ‘ACT’ was identified at position 719 of TP53 ( 15 ).…”