Low frequency of p53 mutations in human thyroid tumors: p53 and Ras mutation in two aut of fifty-six thyroid carcinomas

p53 is a well-known nuclear phosphoprotein encoded by a suppressor 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 severa! neoplasias. Design: In order to investigate the role of p53 mutations in human thyroid tumours, DNA samples derived from fifty-six neoplastic tissues. ranging from benign adenomas to undifferentiated carcinomas, were examined for the presence of p53 gene rnutations. Methods: The analysis has been conducted using polymerase chain reaction (PCR) amplification of the exons 5-9 of the p53 gene followed by single strand conforrnation polymorphism (SSCP) and sequence analyses. Results: One anaplastic carcinoma and one papillary carcinoma showed p53 gene mutations in exons 5 and 8. respectively. A cellline established from the papillary carcinoma showed the same rnutation present in the originai tumour. Both p53 mutations were heterozygous. The pS 3 positive samples were analysed for other genetic alterations frequently detected in human thyroid carcinomas (mutations of the RET, TRK, and ras oncogenes): both p53-mutated sarnples proved to be mutated at leve! of codon 13 of the c-Ki-ras gene. Conclusions: Our data confirrn that p53 gene alterations are rare in well-differentiated thyroid turnours. that they are an important requirement for the establishment in culture of hurnan thyroid carcinoma celllines, and that they can be associated with other genetic alterations. namely ras rnutations, in the rnalignant progression of thyroid turnours.