Correlations between the expression of hTERT and alpha and beta splice variants in human brain tumors

Abstract

Background. Astrocytomas are diffusible infiltrative and aggressive brain tumors that are extensive and heterogeneous clusters of neoplastic growths in the central nervous system (CNS). Meningioma tumors are commonly benign but may demonstrate an invasive pattern with frequent recurrences. Human telomerase reverse transcriptase (hTERT) is an unfavorable prognostic factor for several types of cancers, and there are controversies about its role. Objectives. In the present study, we investigated the relative expression of hTERT splice variants in 2 groups of brain tumors compared to non-tumor samples. Material and methods. The mRNA of 40 brain tumor samples and 4 control samples was extracted; mRNA expression of hTERT alpha-deletion and beta-deletion variants, as well as the wild type isoform, was quantified using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Results. The alpha-deletion variant was significantly expressed in primary benign meningeal tumors (p = 0.01). The results indicate a positive correlation between the relative expression of hTERT mRNA transcript and alpha-deletion and beta-deletion variants in both groups of tumors (meningiomas and astrocytomas). A strong association between the expression of the full-length splice variant and the beta-deletion variant was observed in astrocytoma tumors (p = 0.045). The most significant correlations were found between the hTERT fulllength and beta-deletion variants in high-grade meningiomas (p = 0.018, correlation coefficient (CC) = 0.964) and grade II astrocytomas (p = 0.015; CC = 0.580. In addition, in low grades of both types of tumors, the hTERT full-length variant and especially the alpha-deletion variant were the predominant isoforms. The overexpression of hTERT and beta-deletion variants in high grades of these tumors was statistically significant. Our findings indicate that alpha-deletion and beta-deletion isoforms are associated with high levels of full-length hTERT mRNA in both groups of brain tumor patients. Conclusions. Changes in the splicing pattern of hTERT splice variants in brain tumors and their correlation with pathological alterations in cells could be applied as diagnostic or prognostic biomarkers, or possibly as targets for cancer therapy. However, the function and biological role of hTERT splice variants remain to be clarified.