title: Telomere abnormalities and chromosome fragility in patients affected by familial papillary thyroid cancer.
abstract: BACKGROUND
  Genomic instability has been proposed to play a role in cancer development and can occur through different mechanisms including telomere association and telomere loss. Studies carried out in our unit have demonstrated that familial papillary thyroid cancer (fPTC) patients display an imbalance, at the germinal level, in telomere-telomerase complex.
  
  
  OBJECTIVE
  We aimed to verify whether familial fPTC patients show an increased spontaneous chromosome fragility.
  
  
  METHODS
  To this purpose, we compared telomeric fusions and associations as well as other chromosomal fragility features by conventional and molecular cytogenetic analyses, in phytohemagglutinin stimulated T-lymphocytes from fPTC patients, unaffected family members, sporadic papillary thyroid cancer patients, and healthy subjects.
  
  
  RESULTS
  We demonstrate that fPTC patients have a significant increase in spontaneous telomeric associations and telomeric fusions compared with healthy subjects and sporadic cases in the frame of an otherwise common spontaneous chromosome fragility pattern. A quantitative fluorescence in situ hybridization analysis demonstrates that familial cases display a significant decrease in the telomeric peptide nucleic acid-fluorescence in situ hybridization signal intensity in the metaphase chromosome. Moreover, three copies of the hTERT gene were found only in familial cases, although the result was not statistically significant.
  
  
  CONCLUSIONS
  These results contribute in defining familial thyroid cancer as a clinical entity characterized by an altered telomere stability, which may be associated with the predisposition to develop the familial form of thyroid cancer.
authors.affiliation: Section of Endocrinology and Metabolism, Department of Internal Medicine, Endocrinology and Metabolism, and Biochemistry, University of Siena, Policlinico Santa Maria alle Scotte, Viale Bracci 1, 53100 Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cantara
authors.forename: Milena
authors.initials: M
authors.lastname: Pisu
authors.forename: Daniela Virginia
authors.initials: DV
authors.lastname: Frau
authors.forename: Paola
authors.initials: P
authors.lastname: Caria
authors.forename: Tinuccia
authors.initials: T
authors.lastname: Dettori
authors.forename: Marco
authors.initials: M
authors.lastname: Capezzone
authors.forename: Serena
authors.initials: S
authors.lastname: Capuano
authors.forename: Roberta
authors.initials: R
authors.lastname: Vanni
authors.forename: Furio
authors.initials: F
authors.lastname: Pacini
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma; D002291:Carcinoma, Papillary; D016022:Case-Control Studies; D002478:Cells, Cultured; D019457:Chromosome Breakage; D002873:Chromosome Fragility / Q000235:genetics*; D020732:Cytogenetic Analysis; D005190:Family; D005260:Female; D018628:Gene Dosage; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008677:Metaphase / Q000235:genetics; D008875:Middle Aged; D019098:Telomerase / Q000235:genetics; D016615:Telomere / Q000378:metabolism* / Q000473:pathology; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: C509186:TERT protein, human; D019098:Telomerase