Types And Localisation Of P53 Gene Mutations - A Report On 332 Non-Small Cell Lung Cancer Patients

Mutations of p53 suppressor gene are among the most common molecular abnormalities in human malignancies. We demonstrated earlier significant differences in mutational profiles between NSCLC patients from Poland and Spain. These differences were most probably related to ethnic and/or geographical factors. In the present study we analyzed the types and location of p53 gene mutations in a large group of 332 operated NSCLC patients from two institutions in Northern Poland. Within the last decades this region has been characterized by the highest incidence of lung cancer in Poland. We used both frozen and paraffin-embedded tumor samples and the screened region included exons from 5 to 8. A total of 96 samples (29%) were positive for p53 gene mutation. The proportion of mutations in particular exons was as follows: exon 5-33%, exon 6-22%, exon 7-16%, and exon 8-29%. Three 'hot spots' were located in codons 176, 245 and 248. Evolutionary conserved domains were much more frequently affected than the regions outside domains. The majority of mutations (73%) were missense type, followed by null and silent mutations (21 and 6%, respectively). In all six silent mutations substituted was the third base in codon. There were no major differences in the types and locations of mutations between patients from the two institutions. This homogeneity, together with our earlier findings, may confirm the impact of ethnic and geographical factors on the mutational profile of p53 gene in NSCLC. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.