LOW INCIDENCE OF C-HA-RAS GENE-MUTATIONS IN BENIGN AND MALIGNANT CUTANEOUS LESIONS FROM TRANSPLANT RECIPIENTS

Transplant recipients successively develop benign, pre-malignant and m alignant skin lesions on sun-exposed areas. It has been suggested that UV radiations might induce mutations in ras oncogenes and p53 tumour- suppressor gene, responsible for skin cancers. With PCR and oligoprobe hybridization, we investigated c-Ha-ras gene mutations at codons 12 a nd 61 in 120 cutaneous lesions from grafted patients, since they could represent a marker of the evolution of benign skin lesions towards ma lignancy in this population; 29 similar skin biopsies from non-immunos uppressed patients were also analyzed. In transplant recipients, we de tected mutations at codon 12 only in 1/42 non-melanoma skin cancers an d 2/29 pre-cancerous keratoses. No mutation was detected in 11 cases o f cutaneous Bowen's disease from grafted patients and in pre-malignant and malignant skin samples from control patients. Benign warts exhibi ted an overall incidence of 18% and 15% of mutations at codon 12 of c- Ha-ras gene in grafted and control patients respectively. We detected only one mutation at codon 61 in a plantar wart. Human papillomaviruse s (HPV) are thought to be involved in the malignant evolution of cutan eous disorders in transplant recipients and cooperate with a ras oncog ene to induce malignancy in vitro. The presence of HPV DNA in our seri es of skin samples from grafted patients showed no correlation with th e occurrence of c-Ha-ras mutations. Our findings indicate that c-Ha-ra s-gene activation by mutations is rare in cutaneous lesions from trans plant recipients, and is unlikely to play a crucial role in transforma tion towards malignancy in skin carcinogenesis among grafted patients. (C) 1993 Wiley-Liss, Inc.