Investigation of p53 tumor suppressor gene mutations in patients with a lung mass using sequence analysis [Akciger kitlesi olan hastalarda p53 tümör baskilayici gen mutasyonlarinin sekans analizi ile arastirilmasi]

Objective: The p53 tumour suppressor gene plays an important role in the regulation of cell proliferation. It is located on the short arm of the 17th chromosome. It has 11 exons and encodes for a tumor suppressor protein called p53 which is 53kD in weight and 393 amino acids in length. This protein, a transcription factor, is an important regulator of cell cycle. Up to date, a number of mutations (75 % of which are found between codon 26 and 332) have been detected on p53 gene. Recent researches showed that lung neoplasm resulting from the mutations of p53 gene varied between 33% (adenocarcinoma) and 70% (small cell lung cancer), and it is reported that the hot spots were mainly found at the codons 175, 248, and 273. Material and Methods: In this study, the exons, exon-intron junctions, and some intron regions, which are located between exon 4-9 of p53 gene, of 24 patients who had a surgical operation due to a lung mass were examined by automatic DNA sequencing in University of Leipzig. Results: 53 missense and 7 frameshift mutations were detected between 4th and 9th exons (Codons 36-318) of 18 samples among the 24 samples. Fifty five of these mutations were heterozygous, and five of them were homozygous. Similarly, 12 missense mutations detected as a result of the serial analyses of the region between introns 4-9, and seven of them were heterozygo us and 5 were homozygous. Conclusion: Some research regarding p53 gene reported that codon 175, 248, and 273 were hot spots and mutations were frequent in these codons. However we have not seen any mutations in any of these codons in our study. Nucleotide changes at the positions 13432 (5' beginning) and 13999 (3' ending) of 6th intron, which are very important regions, may result in the formation of an abnormal protein. We suppose that other nucleotide changes are not very important due to their heterozygous nature and location. © 2010 by Türkiye Klinikleri