Volume 2 • Issue 2 • 1000110 Transl Med ISSN: 2161-1025 TM, an open access journal Translational Medicine Javid et al., Transl Med 2012, 2:2 DOI: 10.4172/2161-1025.1000110 Research Article Open Access Clinical and Prognostic Significance of R282W p53 Gene Mutation in North India Patients with Non Small Cell Lung Cancer Jamsheed Javid 1# , M.Masroor 1# , AB Rashid Mir 1# , Imtiyaz Ahamad 1 , Shazia Farooq 1 , Prasant Yadav 1 , Mariyam Zuberi 1 , Sameer Goru 1 , Sheikh shanawaz 1 , P.C Ray 1 , Anant Mohan 2 , Ajaz Ah Bhat 3 , Tanvir S. Khatlani 4 and Alpana Saxena 1 * 1 Department of Biochemistry, Molecular Oncology Lab, Maulana Azad Medical College and Associated Hospitals, New Delhi, India 2 Department of Medicine, All India Institute of Medical Sciences, New Delhi, India 3 Dept of Medicine, Thrombosis Research, Baylor College of Medicine, Houston TX, USA 4 Division of Surgical Oncology, Vanderbilt University, Nashville, TN, USA # Equal contribution of the authors Abstract 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 signifcance of R282W hotspot p53 gene mutation in exon 8, codon 268 (C>T) was studied in hundred clinically confrmed NSCLC patients samples. Sixty two of hundred (62%) cases were reported positive for R282W p53 mutation. The clinically signifcant 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). Signifcantly 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 fndings 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 signifcant 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 infuence the susceptibility, progression of NSCLC patients in Indian population. Large population-based prospective studies are required to validate our fndings. *Corresponding author: Dr. Alpana Saxena, Department of Biochemistry, Molecular Oncology Lab, Maulana Azad Medical College and Associated Hospitals, New Delhi 110002, Tel: +91-9868937401; E-mail: drrashidmamc@gmail.com Received October 05, 2012; Accepted November 13, 2012; Published November 15, 2012 Citation: Javid J, Masroor M, Rashid Mir AB, Ahamad I, Farooq S, et al. (2012) Clinical and Prognostic Signifcance of R282W p53 Gene Mutation in North India Patients with Non Small Cell Lung Cancer. Transl Med 2:110. doi:10.4172/2161- 1025.1000110 Copyright: © 2012 Javid J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Keywords: NSCLC: Non Small Cell Lung Cancer; ADC: Adeno- Carcinoma; SCC: Squamous Cell Carcinoma; ASO: Allele Specifc Oligonucleotide Introduction Non Small Cell Lung Cancer (NSCLC) is the major cancer killer worldwide in both sexes, accounting for >1.2 million deaths each year [1]. As of 2002, the one year prevalence of lung cancer in India for males was 11,511, and the 5 year prevalence was 27,477 accounting for approximately 3% of global prevalence, and 55% of total prevalence in South Central Asia [2]. Te p53 gene, located on the short arm of human chromosome 17, encodes for a nuclear phosphoprotein involved in the regulation of cell proliferation [3]. Te mutant gene product, which tends to accumulate to high levels in cancer cells, is believed to exert a dominant negative efect over coexpressed normal p53. Alterations of either the gene or protein product have turned out to be one of the most common changes identifed in human malignancies. In resected lung cancers, point mutations of the p53 gene have been found in all histologic types, including approximately 45% of resected NSCLC [4,5]. In most studies, it has found that the risk factors of getting lung cancer are related to high percentage of passive smoking [6], cooking oil vapours [7,8] and occupational exposures [9]. Te genetic mistake of p53 in NSCLC, as a result of either p53 protein over-expression [10] or p53 gene mutation [11,12], is found to be strongly correlated with tumor grade and can predict a poor prognosis [13,14]. Te p53 gene is a large gene composed of 11 exons and 10 introns that are made up of 420,000 bp [15,16]. However, 90% of the known mutations exist in exons 4–9, 70% of research studies focusing on exons 5–8. Tis focus is because p53 exons 5–8 code for the DNA-binding domain of the p53 protein, an area where the structure can be highly afected by sequence changes [17]. In solid tumours, p53 gene mutations are generally considered to be a late event in carcinogenesis because they pre- dominate in advanced stages of the disease and have been correlated with short survival in carcinoma of the breast, prostate, lung, and stomach [18,19]. Te main reason why the p53 gene is so frequently mutated in cancers (overall in over 50% of invasive cancers) is that the p53 protein plays multiple, coordinated anti-proliferative roles in response to many diferent types of stress stimuli [4,20]. Te p53 tumor-suppressor gene is commonly mutated in human cancer [21], and 30%–80% of human T r a n s l a ti o n a l M e d i c i n e ISSN: 2161-1025