Mutations in Tumor suppressor TP₅₃ Gene in Formalin- Fixed, Paraffin Embedded Tissues of Squamous Cell Carcinoma (SCC) of Lung Cancer

Abstract

The TP53 gene mutations have been extensively studied in lung cancer and have been used as a means to understand the origin(s) and mechanisms of these mutations in lung cancer development. TP₅₃ gene mutations occur frequently in many human cancers. Analysis of TP53 gene mutations can also provide clues to the etiology of tumor formation. Formalin-fixed, paraffin embedded (FFPE) tissues from patients undergone surgery between 1997 to 2005 were provided the pathology department of Afzalipour Hospital, Kerman, Iran. The mutational status of the exons 5 & 8 of the TP53 gene was screened by PCR followed by sequencing. Of the 25 patient samples sent for sequencing, 22 produced usable results for exon 5 and of these, 18 cases (81.8%) showed mutations. 18 samples also produced usable results for exon 8, and of these, 15 (83.3%) cases contained mutations. We identified a total of 113 mutations in tumor suppressor TP₅₃ gene of squamous cell carcinoma of lung tumors. At least 69 mutations were found in Exon 5 (in 18 cases) and 44 mutations in Exon 8 (in 15 cases). The most frequent mutations in exon 5 were deletion, G to T transvertion, G to A transition, G to C transversion and in exon 8 were A to T and G to T tansversion and deletion. Mutations were spread throughout the exons 5 & 8 but showed a strong preference for some mutational hotspots. These findings showe that TP₅₃ gene mutations contribute to the pathogenesis of non-small cell lung cancer significantly and the frequency of the mutations was higher in Iran compared to other areas described in the literature.