IKKβ overexpression resulted in a striking resistance to skin cancer development and an increased expression of several tumor suppressor proteins, such as p53, p16, and p19.
Finally, we observed that the expression signatures indentified in phenotypically normal cells carrying CDKN2A mutations or MC1R variants are maintained in skin cancer tumors (melanoma and squamous cell carcinoma).
A striking reduction of the permissive histone mark H3K4me3 has been detected in the promoter of P16(INK4a) (4-fold and 9-fold reduction for 10 and 15 weeks UVA-irradiated cells, respectively), which has often been found deregulated in skin cancers.
In this study, we obtained MCCs from 21 elderly patients (19 women, 2 men) and analyzed their DNA for mutation of exons of interest in several tumor-suppressor genes or oncogenes known to be frequently mutated in skin cancer: p53 (exons 4-8), Ras (exons 1 and 2), c-Kit (exon 11), and the INK4a-ARF locus (encoding p14 and p16) (exons 1 and 2).
More specifically, cutaneous melanomas showed a significantly higher proportion of UVB signature mutations at both TP53 and CDKN2A when compared to non-skin cancers using data from their respective locus-specific databases.
Cutaneous and ocular nevi, benign and malignant neoplasms of skin and other sites, brief skin cancer risk assessment tool risk classification for cutaneous melanoma, DNA sequencing of p16INK4a and p14ARF genes, and citations on familial uveal melanoma.
To ascertain whether perturbation of methylation plays a role in such carcinogenesis, the degree of methylation of p53 and p16 gene in DNA obtained from blood samples of people chronically exposed to arsenic and skin cancer subjects was studied.
We examined the frequency of INK4a-ARF, p53, and CDK4 mutations in skin carcinomas from patients with xeroderma pigmentosum (XP), a rare autosomal disease that is associated with a defect in DNA repair and that predisposes patients to skin cancer.
Among these mutations in p16INK4a and p53, 5 of 6 mutations were of the C:G to T:A transitional type; this is known to be related to ultraviolet radiation as previously confirmed in other skin cancers.