Pélisson I, Chardonnet Y, Euvrard S, Schmitt D
INSERM U 346 affiliée CNRS, Hôpital Edouard Herriot, Lyon, France.
Int J Cancer. 1993 Dec 2;55(6):915-20. doi: 10.1002/ijc.2910550607.
Transplant recipients successively develop benign, premalignant 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 DNA 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.
移植受者在阳光暴露部位相继出现良性、癌前和恶性皮肤病变。有人认为紫外线辐射可能诱发ras癌基因和p53肿瘤抑制基因的突变，这些基因与皮肤癌有关。我们采用聚合酶链反应（PCR）和寡核苷酸探针杂交技术，研究了120例移植患者皮肤病变中c-Ha-ras基因第12和61密码子的突变情况，因为这些突变可能代表该人群中良性皮肤病变向恶性病变演变的一个标志物；同时也分析了29例非免疫抑制患者的类似皮肤活检样本。在移植受者中，我们仅在1/42例非黑色素瘤皮肤癌和2/29例癌前角化病中检测到第12密码子的突变。在移植患者的11例皮肤鲍温病以及对照患者的癌前和恶性皮肤样本中均未检测到突变。良性疣中，移植患者和对照患者c-Ha-ras基因第12密码子的突变总体发生率分别为18%和15%。我们仅在1例跖疣中检测到第61密码子的1个突变。人乳头瘤病毒（HPV）被认为与移植受者皮肤疾病的恶性演变有关，并在体外与ras癌基因协同诱导恶性肿瘤。在我们的移植患者系列皮肤样本中，HPV DNA的存在与c-Ha-ras突变的发生无关。我们的研究结果表明，移植受者皮肤病变中因突变导致的c-Ha-ras基因激活很少见，并且不太可能在移植患者皮肤癌发生向恶性转化过程中起关键作用。
