Relation between telomerase activity, hTERT and telomere length for intracranial tumours

Abstract

Abstract. Human linear chromosomes are capped by specialized DNA-protein structures called telomeres. The present study analysed the telomerase activity, hTERT protein and telomere length in meningiomas and gliomas in relation to their WHO grading. Fifty-three freshly dissected tumour biopsies were analysed for telomerase activity, hTERT protein expression and telomere length. Telomerase activity was examined in 41 of the 53 biopsies. Telomerase activity was detected in 3 of 35 (8.6%) screened meningiomas (1 benign, 1 atypical and 1 malignant meningioma). For hTERT expression, 56.4% of meningiomas were positive with a mean labelling index (hTERT LI) of 31.3% (SD=26.5) for the hTERT positive meningiomas. The mean telomere length for meningiomas was 6.983 kb (SD=1.969). For gliomas, no active telomerase was detected in 2 low-grade astrocytomas, whereas three of the four screened glioblastomas were positive for telomerase activity. The only hTERT protein positive astrocytoma had a mean labelling index of 9.0%. On the other hand, the hTERT LI for glioblastomas was 53.6% (SD=28.0). The two low-grade astrocytomas had a telomere length of 14.310 and 9.236 kb. The anaplastic astrocytoma had a telomere length of 4.903 kb and the glioblastomas 5.767 kb (SD=2.042). The normal meningeal and neuronal tissue is negative for telomerase activity and hTERT. The length was ±10.000 kb. These results indicate that telomere shortening may be a critical step in pathogenesis of atypical and malignant meningiomas and gliomas. Critical telomere shortening in vitro was shown to activate telomerase.

The role of TERT-CLPTM1L SNPs, hTERT expression and telomere length in the pathogenesis of oral squamous cell carcinoma

“…telomere shortening as an early event in carcinogenesis (34,37). However, our results are consistent with several previous studies in which longer telomeres have been associated with absence of metastases in OSCC (35), a low grade in intracranial tumors (38), higher overall survival in lung cancer patients (36), and a lower risk of death in patients with prostate tumors (39). Moreover, a lack of correlation between telomere length and clinicopathologic characteristics has also been found in breast (40), colorectal (41), and head and neck (42) tumors.…”

Alterations of telomere length in human brain tumors

“…They found a mean length of 7.165 kb (SD = 1.724) in 34 benign meningioma tumors. The mean telomere length for the three atypical meningiomas was 5.269 kb (SD = 1.107) and 6.472 kb (SD = 4.668) for the two malignant meningiomas [36]. Also, in two low-grade astrocytoma tumors, one sample had mean telomere length of 14.310 kb, while the telomere length for another was 9.236 kb.…”

“…Also, in two low-grade astrocytoma tumors, one sample had mean telomere length of 14.310 kb, while the telomere length for another was 9.236 kb. In one anaplastic astrocytoma and 11 glioblastomas, the mean length of telomeres was 4.903 and 5.767 kb (SD = 2.042), respectively [36]. Finally, they concluded that telomere length cannot be used as a putative prognostic marker as a sole but should be linked with hTERT expression and telomerase activity [36].…”

“…In one anaplastic astrocytoma and 11 glioblastomas, the mean length of telomeres was 4.903 and 5.767 kb (SD = 2.042), respectively [36]. Finally, they concluded that telomere length cannot be used as a putative prognostic marker as a sole but should be linked with hTERT expression and telomerase activity [36]. Based on results of another study, alternative lengthening of telomeres (ALT) is out and away the most powerful prognostic factor yet found for glioblastoma multiform [37].…”

Increased expression of telomere-related proteins correlates with resistance to radiation in human laryngeal cancer cell lines

“…The lower expression level of various factors involved in telomerase activity should impair telomere regeneration at each Sphase (23). Moreover, the altered expression of telomere capping factors might disrupt the capping complex, facilitating telomere degradation and shortening independently of the telomerase status (24,25). This correlates with telomeric damage possibly already appeared in LSCC cells, which may be one of the reasons as to why shortened telomeres result in increased sensitivity to ionizing radiation exposure.…”