title: Short telomeres, telomerase reverse transcriptase gene amplification, and increased telomerase activity in the blood of familial papillary thyroid cancer patients.
abstract: BACKGROUND
  Differentiated papillary thyroid cancer is mostly sporadic, but the recurrence of the familial form has been reported. Short or dysfunctional telomeres have been associated with familial benign diseases and familial breast cancer.
  
  
  OBJECTIVE
  The aim of our work was to study the telomere-telomerase complex in the peripheral blood of patients with familial papillary thyroid cancer (FPTC), including the measurement of relative telomere length (RTL), telomerase reverse transcriptase (hTERT) gene amplification, hTERT mRNA expression, telomerase protein activity, and search of hTERT or telomerase RNA component gene mutations.
  
  
  METHODS
  Cumulating a series of patients seen at the University of Siena and a series at the University of Rome, the experiments were conducted in 47 FPTC patients, 75 sporadic papillary thyroid cancer (PTC) patients, 20 patients with nodular goiter, 19 healthy subjects, and 20 unaffected siblings of FPTC patients.
  
  
  RESULTS
  RTL, measured by quantitative PCR, was significantly (P < 0.0001) shorter in the blood of FPTC patients, compared with sporadic PTCs, healthy subjects, nodular goiter subjects, and unaffected siblings. Also by fluorescence in situ hybridization analysis, the results confirmed shorter telomere lengths in FPTC patients (P = 0.01). hTERT gene amplification was significantly (P < 0.0001) higher in FPTC patients, compared with the other groups, and in particular, it was significantly (P = 0.03) greater in offspring with respect to parents. hTERT mRNA expression, as well as telomerase activity, was significantly higher (P = 0.0003 and P < 0.0001, respectively) in FPTC patients, compared with sporadic PTCs. RTL, measured in cancer tissues, was shorter (P < 0.0001) in FPTC patients, compared with sporadic PTCs. No mutations of the telomerase RNA component and hTERT genes were found.
  
  
  CONCLUSIONS
  Our study demonstrates that patients with FPTC display an imbalance of the telomere-telomerase complex in the peripheral blood, characterized by short telomeres, hTERT gene amplification, and expression. These features may be implicated in the inherited predisposition to develop FPTC.
authors.affiliation: Department of Internal Medicine, University of Siena, Policlinico Santa Maria alle Scotte, 53100 Siena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Capezzone
authors.forename: Silvia
authors.initials: S
authors.lastname: Cantara
authors.forename: Stefania
authors.initials: S
authors.lastname: Marchisotta
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Filetti
authors.forename: Maria Margherita
authors.initials: MM
authors.lastname: De Santi
authors.forename: Benedetta
authors.initials: B
authors.lastname: Rossi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ronga
authors.forename: Cosimo
authors.initials: C
authors.lastname: Durante
authors.forename: Furio
authors.initials: F
authors.lastname: Pacini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000097:blood* / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D002648:Child; D005260:Female; D005784:Gene Amplification / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D019098:Telomerase / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000737:chemistry / Q000502:physiology*; D013964:Thyroid Neoplasms / Q000097:blood* / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D019098:Telomerase