Lack of association of telomerase expression levels with telomere length variation in Lynch syndrome patients.

Abstract

e12527 Background: Anticipation has been reported in Lynch Syndrome (LS) and linked to telomere length shortening. We recently investigated affected carriers (AC) and unaffected carriers (UAC) and found that younger age of onset in AC was associated with shorter telomere lengths. Telomerase activity is important in the maintenance of telomeres. We therefore analysed the expression of the main components of the telomerase complex TERT, TERC and DKC1 in both AC and UAC and assessed their relationship to telomere lengths. Methods: RNA was isolated from peripheral blood mononuclear cells and reverse transcribed to cDNA. Real-time polymerase chain reaction (RT-PCR) was used to quantitate expression levels of TERT, TERC and DKC1. Telomerase expression in AC and UAC was compared and Pearsons correlation coefficient was used to assess relationship between expression of telomerase complex components and telomere length in all patients and subsequently determine if telomerase correlated with age of onset in AC. Results: Thirty AC and 29 UAC were analysed. There was no difference in the mean expression of TERT, TERC and DKC1 between AC and UAC (p = 0.60, 0.27, 0.32). Furthermore telomerase expression did not correlate with telomere length in either group and in AC there was no relationship between telomerase expression and age of onset malignancy despite patients with shorter telomeres having earlier onset malignancies. Conclusions: Differences in telomere lengths in AC cannot be explained by altered telomerase expression. The maintenance of telomeres in Lynch Syndrome patients may be due to an alternate pathway.