P40 Aberrant epigenetic and genetic TP53 novel translational expression of codon 240 (Ser240Thr) – Association with squamous cell carcinoma of head and neck

Abstract

Head and neck cancers usually begin in squamous cells that line the moist, mucosal surfaces inside the mouth, nose, and throat. These squamous cell cancers are often referred to as squamous cell carcinomas of the head and neck. Oral squamous cell carcinoma (OSCC) is the major risk factor of head and neck cancer in developing countries like Pakistan. The main cause OSCC is considered to be the excessive chewing habit of paan, chhaliya, tobacco, niswar, gutka and manpuri these days. Mutagens can damage DNA and generate promutagenic lesions. It has been reported that exon 4–9 were the hot spots of the mutation in the tumor suppressor gene. This study aims to find out the loss of TP53 functions due to mutation/polymorphism caused by genomic alteration and interaction with tobacco and its related ingredients in Pakistan. A total of 260 OSCC patient’s tissues and blood specimens were collected with informed consent from local hospitals of Karachi. Mutations in exons 2–11 of p53 gene were examined by polymerase chain reaction and single stranded conformational polymorphisms (PCR-SSCP) and directly sequenced. The current study revealed a novel mutation in exon 7 of p53 gene. This mutation was observed only in the tumors of the OSCC patients. The “AGT” to “ACT” missense mutation was identified at position 719 at TP53. This change substitutes the amino acid serine with threonine at position 240 of p53 protein, suggesting that the training allele of the p53 gene is associated with mutation in conserved region. This novel missense 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 cellular processes and p53 protein function.