Molecular genetic alterations of FHIT and p53 genes in benign and malignant thyroid gland lesions

Pavelić, Krešimir and Dedivitis, Rogerio A. and Kapitanović, Sanja and Čačev, Tamara and Guirado, Cristiano R. and Danić, Davor and Radošević, Senka and Brkić, Kornelije and Pegan, Boris and Križanac, Šimun and Kusić, Zvonko and Spaventi, Šime and Bura, Miljenko (2006) Molecular genetic alterations of FHIT and p53 genes in benign and malignant thyroid gland lesions. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 599 (1-2). pp. 45-57. ISSN 0027-5107

Preview

PDF - Accepted Version Download (1MB) | Preview

Abstract

Several oncogenes and tumor-suppressor genes are involved either as early or late event in thyroid gland carcinogenesis. Human FHIT (fragile histidine triad) gene is highly conserved gene whose loss of function may be important in the development and/or progression of various types of cancer. We undertook this study to analyze FHIT and p53 gene status in different benignant and malignant thyroid tumors. Status of these genes as well as intensity of apoptosis was analyzed in tumor tissues by molecular genetic methods, immunohistochemistry, and FACS-scan analysis. The majority of the malignant thyroid cancers displayed aberrant expression of FHIT gene, concominant with p53 gene inactivation. This is followed by low rate of apoptosis, which may be important in the development and/or progression of thyroid cancer. We found higher incidence of p53 mutation and aberrant processing of FHIT mRNA in malignant tumors (papillary, follicular, medullary and anaplastic carcinomas) and i! n those tumors with distant metastasis. The growth of p53(-)/FHIT- follicular carcinoma of human origin was much faster in nude mice than p53(+)/FHIT- follicular carcinoma, and mice had shorter survival rate. Our results show a correlation between aberrant FHIT and p53 expression, low rate of apoptosis, and malignancy. Concomitant aberration of FHIT gene and p53 could be responsible for development of highly malignant types of thyroid cancer and may be considered as a prognostic marker for these tumors.

Actions (login required)

View Item

Downloads