The mutation pattern detected in the Tg skin lesions closely resembles that detected in human NMSC, with the highest mutation rate in p53 and Notch genes.
As MMR enzyme hMSH2 displays a p53 target gene, is induced by UVB radiation and is involved in NER pathways, studies have now been initiated to elucidate the physiological and pathophysiological role of MMR in malignant melanoma and nonmelanoma skin cancer development.
This report shows that much of the 682-gene signature of this murine skin carcinoma transcriptome is also present in breast and lung cancer mouse models in which p53 is inhibited.
Epidemiology studies have implicated Tp53 mutations triggered by UV exposure, and human papilloma virus (HPV) infection to be significant causes of non-melanoma skin cancer.
In total, there was no significant difference in the p53 codon 72 genotypes between histological types of NMSC, gender, race, tumor location and age group.
In 902 cases of basal cell carcinoma (BCC), 676 cases of squamous cell carcinoma (SCC) and 812 controls, no association was found between the TP53 polymorphism and risk of non-melanoma skin cancer [odds ratio (OR)(BCC) 0.98, 95% confidence interval (CI) 0.80-1.20; OR(SCC) 0.93, 95% CI 0.75-1.16].
We observed abnormal p53 accumulation in over half of the samples analysed (55.5%), suggesting it to be a major part of the carcinogenic process of NMSC; however; there was no association between p53 positivity and the presence of mtDNA mutations (P = 0.47).
Moreover, we propose up-regulated wild-type p53 together with p76(MDM2) as major players in the control of DNA damage/repair and prevention of photodamage and nonmelanoma skin cancer in vitiligo.
The mechanism by which the E6 protein of cutaneous HPV types interacts with cellular proteins to induce either benign or malignant cutaneous lesions, has not been elucidated, although extensive ultraviolet exposure and mutated p53 (hot-spot mutations) are known to be associated with non-melanoma skin cancer.
As MMR enzyme hMSH2 displays a p53 target gene, is induced by UVB radiation and is involved in NER pathways, studies have now been initiated to elucidate the physiological and pathophysiological role of MMR in malignant melanoma and nonmelanoma skin cancer development.
Alterations of the p53 tumor suppressor gene are very common in non-melanoma skin cancer, and dysregulation of p53 pathways appear to be an early event in the tumor development.
Of these, thickness, male sex, dense freckling, low nevus density on the back, histologic subtype and history of nonmelanoma skin cancer appeared to be independently associated with strong p53 staining.
This study's data suggest that psoralen + ultraviolet A-induced p53 mutations may play an important part in the development of nonmelanoma skin cancer in psoralen + ultraviolet A-treated patients, but these mutations are likely to act in concert with the effects of other carcinogenic exposures, particularly ultraviolet B, in the development of skin cancer.
We also found a significant association between p53-72R homozygosity and nonmelanoma skin cancer in renal transplant recipients (basal cell carcinoma, p < 0.01; squamous cell carcinoma, p < 0.05) but not in immunocompetent patients compared with skin type matched controls. p53 sequence data revealed mutations in 30 of 70 (42.9%) nonmelanoma skin cancers, 28 (93%) of which were in the p53-72R allele.