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Clinical and Prognostic Significance of R282W p53 Gene Mutation in North India Patients with Non Small Cell Lung Cancer

Jamsheed Javid, M.Masroor, AB Rashid Mir, Imtiyaz Ahamad, Shazia Farooq, Prasant Yadav, Mariyam Zuberi, Sameer Goru, Sheikh shanawaz, P.C Ray, Anant Mohan, Ajaz Ah Bhat, Tanvir S. Khatlani and Alpana Saxena*

Background: p53 plays a central role in protecting the integrity of the genome. Its activity is ubiquitously lost in cancers, either by inactivation of its protein (p53 pathway) or by mutation in the p53 gene, thereby indicating its importance in understanding cancer and as a therapeutic target. Given the high frequency of the hotspot R282W p53 gene mutation in our NSCLC patients, we have evaluated the association of R282W mutation with the progression of the malignancy.
Methods: Blood DNA was extracted from cases. The R282W hotspot p53 gene mutation was detected by using ASO-PCR. Most of the NSCLC patient’s submitted samples for EGFR gene mutation analysis.
Results: The clinical significance of R282W hotspot p53 gene mutation in exon 8, codon 268 (C>T) was studied in hundred clinically confirmed NSCLC patients samples. Sixty two of hundred (62%) cases were reported positive for R282W p53 mutation. The clinically significant difference was reported between early and the advanced stages (72% vs. 43%) (p<0.007). Similarly higher frequency of this mutation was reported in adenocarcinoma (76.08%) than
squamous cell carcinoma 27 (50%) (p<0.0134). Significantly higher frequency of R282W p53 mutation was reported in distant metastasis 23 (85.18%) than the metastasis (<0.0075), current smokers than the ex smokers (p=0.02).
These findings suggest that stage, smoking, histological type, metastasis is strongly associated with the incidence of R282W mutation. Other variables as gender, age, smoking level, and family history of any cancer does not showing any significant association with p53, R282W mutation. Slightly lower overall survival was reported in NSCLC patients with R282W mutation than wild p53 cases (p<0.049).
Conclusion: Our results suggest that the hotspot R282W p53 mutation may influence the susceptibility,
progression of NSCLC patients in Indian population. Large population-based prospective studies are required to validate our findings.