Low frequency of p53 mutations in human thyroid tumors; p53 and Ras mutation in two out of fifty-six thyroid tumours

Domenico Salvatore, Angela Celetti, Nicole Fabien, Christian Paulin, Maria Luisa Martelli, Caterina Battaglia, Daniela Califano, Carmen Monaco, Giuseppe Viglietto, Massimo Santoro, Alfrede Fusco

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: 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 several 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 mutations. 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 conformation polymorphism (SSCP) and sequence analyses. Results: One anaplastic carcinoma and one papillary carcinoma showed p53 gene mutations in exons 5 and 8, respectively. A cell line established from the papillary carcinoma showed the same mutation present in the original tumour. Both p53 mutations were heterozygous. The p53 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 samples proved to be mutated at level of codon 13 of the c-Ki-ras gene. Conclusions: Our data confirm that p53 gene alterations are rare in well-differentiated thyroid tumours, that they are an important requirement for the establishment in culture of human thyroid carcinoma cell lines, and that they can be associated with other genetic alterations, namely ras mutations, in the malignant progression of thyroid tumours.

Original languageEnglish
Pages (from-to)177-183
Number of pages7
JournalEuropean Journal of Endocrinology
Volume134
Issue number2
Publication statusPublished - Feb 1996

ASJC Scopus subject areas

  • Endocrinology

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