Clinical implications of cytosine deletion of exon 5 of P53 gene in non small cell lung cancer patients

Abstract

Aim:Lung cancer is considered to be the most common cancer in the world. In humans, about 50% or more cancers have a mutated tumor suppressor p53 gene thereby resulting in accumulation of p53 protein and losing its function to activate the target genes that regulate the cell cycle and apoptosis. Extensive research conducted in murine cancer models with activated p53, loss of p53, or p53 missense mutations have facilitated researchers to understand the role of this key protein. Our study was aimed to evaluate the frequency of cytosine deletion in nonsmall cell lung cancer (NSCLC) patients.Methods:One hundred NSCLC patients were genotyped for P53 (exon5, codon168) cytosine deletion leading to loss of its function and activate the target genes by allele-specific polymerase chain reaction. The P53 cytosine deletion was correlated with all the clinicopathological parameters of the patients.Results and Analysis:59% cases were carrying P53 cytosine deletion. Similarly, the significantly higher incidence of cytosine deletion was reported in current smokers (75%) in comparison to exsmoker and nonsmoker. Significantly higher frequency of cytosine deletion was reported in adenocarcinoma (68.08%) than squamous cell carcinoma (52.83%). Also, a significant difference was reported between p53 cytosine deletion and metastasis (64.28%). Further, the majority of the cases assessed for response carrying P53 cytosine deletion were found to show faster disease progression.Conclusion:The data suggests that there is a significant association of the P53 exon 5 deletion of cytosine in codon 168 with metastasis and staging of the disease.

Correlation between Programmed Death-1 Ligand-1 and p53 in Patients with Lung Adenocarcinoma

“…On the other hand, p53 is the most frequently studied molecular mutation in human cancer, and p53 protein expression has been found in more than 50% of human tumors. The p53 is a tumor suppressor gene, which plays a negative regulatory role in cell proliferation and differentiation,[ 4 5 ] thus suggesting that aberrant p53 expression is a prerequisite for tumor development.…”

Evaluation of efficacy and safety for recombinant human adenovirus-p53 in the control of the malignant pleural effusions via thoracic perfusion

“…It locates on the short arm of human chromosome 17 and encodes a nuclear phosphoprotein4. It is reported that the p53 gene is mutated in 50% to 70% of patients with lung cancer5, which plays a crucial function in cell cycle regulation, genomic stability, stress induced reaction and DNA repairing4.…”

“…It locates on the short arm of human chromosome 17 and encodes a nuclear phosphoprotein4. It is reported that the p53 gene is mutated in 50% to 70% of patients with lung cancer5, which plays a crucial function in cell cycle regulation, genomic stability, stress induced reaction and DNA repairing4. The point mutations on exons 3–9 and 5–8 are mainly common mutations of p53 gene in lung cancer; especially the point mutation on exons 5–8, has been observed in 40–50% of non-small cell lung cancer (NSCLC)6.…”