Loss of heterozygosity and p53 expression in Pterygium

While the pathogenesis of pterygium is still not well understood, environmental factors such at UV light, appear to play an important role in its development. UV radiation can cause mutations in genes such as the p53 tumor suppressor gene, that when inactivated through mutation and loss of heterozygosity can lead to cell proliferation and genomic instability. However, aside from mutations in the gene, other mechanisms have been identified that can lead to loss of p53 function. These include the interaction of the p53 protein with cellular or viral gene products that lead to the inactivation of p53 or to its rapid degradation as well as the silencing of transcription of the p53 gene through the aberrant expression of factors that control p53 expression. We have analyzed the status and expression of the p53 gene in epithelial cells derived from pterygium and have demonstrated that the p53 gene has undergone a monoallelic deletion. Assays for both p53 protein and mRNA revealed that the remaining allele in these cells is not expressed at detectable levels. Furthermore, the remaining allele, by DNA sequence analysis appears to remain wild type. The mechanism of silencing the p53 gene and the loss of p53 expression in these cells is currently under investigation.