Repozitorij Medicinskog fakulteta Sveučilišta u Zagrebu

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

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    English 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.

    Item Type: Article
    MeSH: Acid Anhydride Hydrolases - genetics - metabolism ; Genes, p53 ; Mutation ; Neoplasm Proteins - genetics - metabolism ; Thyroid Diseases - genetics - metabolism - pathology ; Thyroid Neoplasms - genetics - metabolism - pathology ; Adolescent ; Adult ; Aged ; Animals ; Apoptosis ; Female ; Flow Cytometry ; Gene Expression ; Humans ; Immunohistochemistry ; Loss of Heterozygosity ; Male ; Mice ; Mice , Nude ; Middle Aged ; Molecular Biology ; Neoplasm Transplantation ; Transplantation, Heterologous
    Divisions: Katedra za otorinoloringologiju s audiologijom i fonijatrijom
    Katedra za radiologiju i opću kliničku onkologiju
    Katedra za patologiju
    Depositing User: Slaven Semper
    Status: Published
    Pavelić, Krešimir
    Dedivitis, Rogerio A.
    Kapitanović, Sanja
    Čačev, Tamara
    Guirado, Cristiano R.
    Danić, Davor
    Radošević, Senka
    Brkić, Kornelije
    Pegan, Boris
    Križanac, Šimun
    Kusić, Zvonko
    Spaventi, Šime
    Bura, Miljenko
    Date: 25 July 2006
    Date Deposited: 19 Mar 2007
    Last Modified: 23 Sep 2011 18:09
    Subjects: /
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