Meningiomas, dicentric chromosomes, gliomas, and telomerase activity

Lack of telomere maintenance during cell replication leads to telomere eros ion and loss of function. This can result in telomere associations which pr obably cause the dicentric chromosomes seen in some tumour cells. One mecha nism of telomere maintenance in dividing cells is the action of telomerase, a ribonucleoprotein enzyme that adds TTAGGG repeats onto telomeres and com pensates for their shortening during cell division. Over 90 per cent of ext racranial malignant neoplasms have been found to have telomerase activity. This study sought to determine if there was a relationship between absence of telomerase activity and presence of dicentric chromosomes in meningiomas and to what extent the other main group of central nervous system tumours, the gliomas, expressed telomerase activity, Telomerase activity was measur ed on 25 meningiomas and 29 gliomas, Four of the meningiomas were atypical variants and 11 were positive for dicentric chromosomes. Twenty-live of 29 gliomas were glioblastoma multiforme tumours, Measures were taken to ensure absence of false positives due to primer-dimer interaction and false negat ives due to protein degradation or the presence of Tag polymerase inhibitor s. All 25 meningiomas and the four low-grade gliomas (WHO grade II) were te lomerase activity-negative. Seven (28 per cent) of the 25 glioblastoma mult iforme tumours showed telomerase activity. The absence of telomerase activi ty in meningiomas and the high frequency of telomere associations support t he hypothesis that these tumours are benign, transformed but pre-crisis. Th e relatively low frequency of telomerase activity in the malignant glioblas toma multiforme suggests that most of these tumours may have other mechanis ms of telomere maintenance and that the potentially therapeutic telomerase inhibitors will not be of great value in the future management of the major ity of patients suffering from these tumours, Copyright (C) 1999 John Wiley & Sons, Ltd.