LOW-FREQUENCY OF P53 MUTATIONS IN HUMAN THYROID-TUMORS - P53 AND RAS MUTATION IN 2 OUT OF 56 THYROID-TUMORS

Objective: p53 is a well-known nuclear phosphoprotein encoded by a sup pressor gene known to be mutated in various kinds of human tumours. A relationship between p53 gene mutation and tumour progression seems to be a common feature of several neoplasias. Design: In order to invest igate the role of p53 mutations in human thyroid tumours, DNA samples derived from fifty-six neoplastic tissues, ranging from benign adenoma s to undifferentiated carcinomas, were examined for the presence of p5 3 gene mutations, Methods: The analysis has been conducted using polym erase chain reaction (PCR) amplification of the exons 5-9 of the p53 g ene followed by single strand conformation polymorphism (SSCP) and seq uence analyses. Results: One anaplastic carcinoma and one papillary ca rcinoma showed p53 gene mutations in exons 5 and 8, respectively. A ce ll line established from the papillary carcinoma showed the same mutat ion present in the original tumour, Both p53 mutations were heterozygo us. The p53 positive samples were analysed for other genetic alteratio ns frequently detected in human thyroid carcinomas (mutations of the R ET, TRK, and ras oncogenes): both p53-mutated samples proved to be mut ated at level of codon 13 of the c-Ki-ras gene. Conclusions: Our data confirm that p53 gene alterations are rare in well-differentiated thyr oid tumours, that they are an important requirement for the establishm ent in culture of human thyroid carcinoma cell lines, and that they ca n be associated with other genetic alterations, namely ras mutations, in the malignant progression of thyroid tumours.