Polymorphisms and mutatons detected in P53 exon 2 and intron 2 in lung carcinomas in Hong Kong

Abstract

Purpose: Lung cancer is the commonest cause of cancer death in both men and women in Hong Kong, and over 60% of our female patients are non-smokers. Gene mutations are involved in the multistage process of lung tumorigenesis. p53 gene mutations with ethnic differences have been reported. In our previous study of 52 non-small cell lung carcinoma (NSCLC) patients, a polymorphism in p53 intron 2 (A1 and A2 alleles) and a 15% frequency of p53 intron 2 mutations were detected. In the present study, the significance of these polymorphisms and mutations was further studied. Methods: Triple specimens from the lung tumour, normal lung tissue and peripheral blood of 23 NSCLC patients were analysed for polymorphisms and mutations in p53 gene intron 2 and exons 2 and 3 by polymerase chain reaction - single strand conformation polymorphism and direct DNA-sequencing techniques. Results: All cell lines established from peripheral blood lymphocytes shared the same genotypes found in the normal lung tissue, but differed in 4 cases where mutations were detected in the tumours. Detected mutations in the tumour tissues resulted from an A2 to A1 conversion. The A1 allelic frequency appeared to be specifically and significantly increased in the adenocarcinoma tumour tissues as compared to normal tissues in these patients. A new polymorphism localized to p53 exon 2 was detected, appearing with equally high frequency among lung cancer patients and healthy individuals. Conclusions: The p53 intron 2 polymorphic locus is a hot spot for mutations in Hong Kong lung cancer patients and these mutations are probably somatic. Clinical Implications: p53 gene is a commonly affected target gene in our NSCLC patients, and intron 2 mutations may play a role in the malfunction of p53 gene during lung carcinogenesis in Chinese patients in Hong Kong. Peripheral blood DNA may be used to analyse the normal genotype of this locus. The clinical significance of the new p53 polymorphism in exon 2 remains to be elucidated.