Abstract
Background: Differentiated non-medullary thyroid cancer (NMTC) is mostly sporadic, but the recurrence of familial form of the disease has been reported. Short or dysfunctional telomeres have been associated with familial benign diseases and familial breast cancer.
Aims: To study the telomere-telomerase complex in familial NMTC (FNMTC).
Materials: Genetic analysis included the measurement of relative telomere length (RTL), telomerase reverse transcriptase (hTERT) gene amplification, telomerase protein activity and search of TERC (telomerase RNA component) mutations. These experiments were conducted in 29 FNMTC patients, 50 sporadic papillary thyroid cancer (PTC) patients, 20 patients with nodular goiter, 19 healthy subjects, and in 10 unaffected siblings of FNMTC patients.
Results: RTL was significantly (p<0.0001) shorter in FNMTC patients compared to sporadic PTC, healthy subjects, nodular goiter and unaffected siblings. hTERT gene amplification was found in FNMTC patients compared to the other groups (p><0.0001) and, it was significantly (p><0.02) greater in patients of the 2nd generation than those of the 1st generation. Compared to control groups, FNMTC had increased activity of functional telomerase, whose levels were not different in the first and the second generation. In FNMTC patients hTERT gene amplification was inversely correlated (p><0.0001) with RTL and positively correlated with hTERT activity. No mutations of the TERC gene were found.
Conclusion: Our study demonstrates that patients with FNMTC display an imbalance of the telomere-telomerase complex, characterized by short telomeres, hTERT gene amplification and high telomerase activity. These features may be implicated in the inherited predisposition to develop FNMTC.