Mutation analysis of P73 and TP53 in Merkel cell carcinoma

The p73 gene has been mapped to 1p36.33, a region which is frequently delet ed in a wide variety of neoplasms including tumours of neuroectodermal orig in, The p73 protein shows structural and functional homology to p53. For th ese reasons, p73 was considered as a positional and functional candidate tu mour suppressor gene. Thus far, mutation analysis has provided no evidence for involvement of p73 in oligodendrogliomas, lung carcinoma, oesophageal c arcinoma, prostatic carcinoma and hepatocellular carcinoma. In neuroblastom a, two mutations have been observed in a series of 140 tumours. In view of the occurrence of Ip deletions in Merkel cell carcinoma (MCC) and the locat ion of p73 we decided to search for mutations in the p73 gene in five MCC c ell lines and ten MCC tumours to test potential tumour suppressor function for this gene in MCC. In view of the possible complementary functions of p7 3 and TP53 we also examined the status of the TP53 gene. Sequence analysis of the entire coding region of the p73 gene revealed previously reported po lymorphisms in four MCCs, In one MCC tumour, a mis-sense mutation located i n the NH2-terminal transactivation region of the p73 gene was found. These results show that p73, analogous to neuroblastoma, is infrequently mutated in MCC. This is also the first report in which the role of TP53 in MCC has been investigated by sequencing the entire coding region of TP53. TP53 mis- sense mutations and one non-sense mutation were detected in three of 15 exa mined MCCs, suggesting that TP53 mutations may play a role in the pathogene sis or progression of a subset of MCCs, Moreover, typical UVB induced C to T mutations were found in one MCC cell line thus providing further evidence for sun-exposure in the aetiology of this rare skin cancer. (C) 2000 Cance r Research Campaign.