Mutation Analysis of Exon 23 of the PTCH Tumor Suppressor Gene in Multiple Basal Cell Carcinoma Patients with a History of Radiodermatitis

Abstract

Background: Basal Cell Carcinoma (BCC) with slow-growing and rarely metastasise character is the most common human neoplasm. Multiple BCCs is mostly raised from germline mutations in the tumour suppressor gene, PTCH with a genetically transmission pattern. Multiple BCCs, as well may be originated from radiodermatitis which is a significant side effect of ionizing radiation exposure delivered to the skin in different skin treatments. PTCH is a critical member of the Sonic Hedgehog signalling pathway and its mutations reported as an important event in 40 to 80 % of skin cancers. The exon number 23 is a critical exon in the function of PTCH protein. Mutations are reported in codon 1315 of PTCH in non-melanoma skin cancers. Methods: We assessed the mutations in exon 23 of PTCH gene by polymerase chain reaction and direct sequencing in peripheral blood cells from 10 patients with multiple BCCs. All of the subjects were selected among whom had a history of radiation exposure and subsequent radiodermatitis. Results: Direct sequencing revealed a Cytosine to Thymine mutation in codon 1315 of the PTCH gene in 60% of the patients, from which 50% detected as heterozygotes with both of the C and T allele and 10% were homozygotes for T allele in the same position. Four subjects (40%) were detected as normal homozygotes of C allele, same as the normal population. Conclusion: The mutations with ID: rs 3575564 were detected in codon 1315 which transform the proline amino acid to leucine in the PTCH protein. This transformation may affect the normal function of the PTCH protein as reported previously. Patients with multiple BCC who had a history of radiation exposure show a transformation from Cytosine to Thymine in codon number 1315 of PTCH gene in their peripheral blood cells. Subsequent assessment of the BCC tissues will clarify the somatic mutagenesis effects of the radiation.