Low incidence of C‐Ha‐ras gene mutations in benign and malignant cutaneous lesions from transplant recipients

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Abstract
Transplant recipients successively develop benign, pre‐malignant and malignant 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 and 61 in 120 cutaneous lesions from grafted patients, since they could represent a marker of the evolution of benign skin lesions towards malignancy in this population; 29 similar skin biopsies from non‐immunosuppressed patients were also analyzed. In transplant recipients, we detected mutations at codon 12 only in 1/42 non‐melanoma skin cancers and 2/29 pre‐cancerous keratoses. No mutation was detected in 11 cases of cutaneous Bowen's disease from grafted patients and in pre‐malignant and malignant skin samples from control patients. Benign warts exhibited 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 papillomaviruses (HPV) are thought to be involved in the malignant evolution of cutaneous disorders in transplant recipients and cooperate with a ras oncogene to induce malignancy in vitro. The presence of HPV ONA in our series of skin samples from grafted patients showed no correlation with the occurrence of c‐Ha‐ras mutations. Our findings indicate that c‐Ha‐ras‐gene activation by mutations is rare in cutaneous lesions from transplant recipients, and is unlikely to play a crucial role in transformation towards malignancy in skin carcinogenesis among grafted patients.