Involvement of p53 and p16 tumor suppressor genes in recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma

Recessive dystrophic epidermolysis bullosa (RDEB) is an autosomal recessive disorder characterized by the loss of collagen type VII, an intrinsic component of the anchoring fibrils, which attach the epidermis to the dermis. Of the genetic blistering disorders, RDEB has the highest rate of morbidity and mortality, with morbidity arising from fusion of digits in a mitten-glove deformity and growth retardation associated with anemia. The leading cause of death in RDEB is cutaneous squamous cell carcinoma, which causes death through invasion and metastasis. In order to better understand the pathogenesis of these rare but aggressive squamous cell carcinoma (SCC), we analyzed them for mutations in p53 and loss of p16ink4a. Three tumors demonstrated mutations in the p53 tumor suppressor gene. We also analyzed SCC from patients with RDEB for the presence of p16ink4a hypermethylation, and found two tumors that have loss of p16ink4a through hypermethylation. This is the first description of specific abnormalities in tumor suppressor genes in RDEB associated SCC, and demonstrates that alterations in both p53 and p16ink4a can contribute to RDEB associated SCC.