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

Background: Basal Cell Carcinoma (BCC) with its slow-growing and rarely metastatic nature is the most common human neoplasm. Multiple BCCs mostly result from germline mutations in the tumor suppressor gene, PTCH with a genetic transmission pattern. Multiple BCCs may also originate from radiodermatitis which is a significant side effect of ionizing radiation exposure delivered to the skin in various skin treatments. PTCH is a critical member of the Sonic Hedgehog signalling pathway and mutations in this gene have been reported in as many as 40-80% of skin cancers. Exon number 23 is a critical exon in the function of the PTCH protein. Mutations have been reported in codon 1315 of PTCH in non-melanoma skin cancers. Methods: We assessed mutations in exon 23 of the PTCH gene by polymerase chain reaction and direct sequencing in the peripheral blood cells of 10 patients with multiple BCCs. All of the subjects were selected from among patients with 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 patients, 50% of which were heterozygotes, possessing both the C and T allele, and 10% were homozygotes for the T allele in the same position. Four subjects (40%) were normal homozygotes of the C allele, similar to the normal population. Conclusion: 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 BCCs who had a history of radiation exposure show a transformation from cytosine to thymine in codon number 1315 of the PTCH gene in their peripheral blood cells. Subsequent assessment of BCC tissues will clarify the somatic mutagenesis effects of radiation.