title: Molecular genetic alterations of FHIT and p53 genes in benign and malignant thyroid gland lesions.
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 in 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.
authors.affiliation: Division of Molecular Medicine, Ruder Bosković Institute, Zagreb, Croatia. pavelic@irb.hr
authors.forename: Kresimir
authors.initials: K
authors.lastname: Pavelić
authors.forename: Rogerio A
authors.initials: RA
authors.lastname: Dedivitis
authors.forename: Sanja
authors.initials: S
authors.lastname: Kapitanović
authors.forename: Tamara
authors.initials: T
authors.lastname: Cacev
authors.forename: Cristiano R
authors.initials: CR
authors.lastname: Guirado
authors.forename: Davor
authors.initials: D
authors.lastname: Danić
authors.forename: Senka
authors.initials: S
authors.lastname: Radosević
authors.forename: Kornelije
authors.initials: K
authors.lastname: Brkić
authors.forename: Boris
authors.initials: B
authors.lastname: Pegan
authors.forename: Simun
authors.initials: S
authors.lastname: Krizanac
authors.forename: Zvonko
authors.initials: Z
authors.lastname: Kusić
authors.forename: Sime
authors.initials: S
authors.lastname: Spaventi
authors.forename: Miljenko
authors.initials: M
authors.lastname: Bura
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D008967:Molecular Biology; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D013959:Thyroid Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase