Comparison of TP53 mutation analysis findings for tar pitch dermatopathy and ionizing radiation-related skin cancer

Background: Tar has been well known as a carcinogen ever since Yamagiwa artificially induced carcinogenesis for the first time by painting a rabbit ear with tar 100 years ago. While humans can be exposed to tar under numerous circumstances, few molecular pathological analyses of skin lesions caused by "tar pitch dermatopathy" have been performed because tar pitch dermatopathy itself is currently rare. Methods: A mutation analysis of TP53 was conducted using long-term stored formalin-fixed, paraffin-embedded tissue specimens of tar pitch dermatopathy in 4 subjects; a similar analysis of radiation-induced skin cancer in 2 subjects was also performed for comparison. Multiple sites were analyzed. Results: Among the specimens from the 4 subjects with tar pitch dermatopathy, the mutations c.625A>T and c.715A>G were each found in 1 of the lesion specimens, whereas the wild type for TP53 was seen in all the non-tumorous skin samples from these cases. The additional mutation c.503A>C was also detected in a different portion of the specimen from the case in which c.715A>G had been detected. In contrast, in 1of the 2 cases with radiation-induced skin cancer (3 squamous cell carcinoma lesions), the novel mutations c.224delC and c.470delT were found at dipyrimidine sites of TP53 . Thus, the mutation spectrum found in tar pitch dermatopathy did not include G>T transversions arising from benzo(a)pyrene, as expected, but instead included the mutation c.625A>T, which is prevalent among tobacco-related cancers according to the IARC database. Conclusions: Skin malignancy developing under peculiar conditions provides an opportunity to investigate the human reality of environmental carcinogenesis. Although a small piece of data this information will be helpful for understanding human skin carcinogenesis in terms of occupational exposure to environmental substances and informative in precision medicine especially in precision prevention.