TELOMERASE ACTIVITY AND ALTERATIONS IN TELOMERE LENGTH IN HUMAN BRAIN-TUMORS

Telomerase activity was examined in 170 human brain tumor tissues, and terminal restriction fragment (TRF) length was examined in 152 of the 170. Telomerase activity was detected in 61.7% (66 of 107) of the neu roepithelial tumors. However, the detection rates of telomerase activi ty were widely different for different histopathological entities. In the case of astrocytic tumors, the detection rate was 20.0% (3 of 15) for grade II astrocytomas, 40.0% (6 of 15) for anaplastic astrocytomas , and 72.3 % (33 of 47) for glioblastomas. The mean TRF length of the tumors with telomerase activity was significantly shorter than that of the tumors with undetectable telomerase activity for each tumor entit y. In grade II and anaplastic astrocytomas, telomerase activity was an indicator of early histological progression and reduced survival of t he patients, although there was no difference in MIB-1 staining indice s between the tumors with and without telomerase activity at onset. In three astrocytic tumors, concurrence of telomere shortening and telom erase reactivation was observed at recurrence; in these cases, tumors progressed to a higher grade. Ten glioblastomas that progressed from l ower-grade tumors exhibited telomerase activity, and their TRF lengths were reduced in 80% (8 of 10). In contrast, telomerase activity was d etected in only 63.3% (19 of 30; P < 0.05) and the TRF length remained compatible with normal values in 56.7% (17 of 30; P < 0.01) of de nov o glioblastomas, Thus, telomerase activity strongly correlated with po tential tumor progression in the short term as well as with progressio n itself of the astrocytic tumors, whereas telomeres may still have be en in the process of shortening in some of the de novo glioblastomas. High telomerase activity was exhibited in all primitive neuroectoderma l tumors, anaplastic oligoastrocytomas, neuroblastomas, and oligodendr ogliomas, TRF length was reduced in the majority (14 of 15) of three p reviously high-grade tumors, whereas it was compatible with that of no rmal brain tissues in the oligodendrogliomas, suggesting that telomera se activity with shortened telomeres correlates with the aggressive gr owth of high-grade neuroepithelial tumors. Tumor cell lines could be e stablished from 17.2% (5 of 29) of neuroepithelial tumors with telomer ase activity but not from tumors without this activity (P < 0.05), sug gesting that telomerase reactivation is an essential event in the neur oepithelial cell immortalization iio vitro. In nonneuroepithelial tumo rs, telomerase activity was detected in malignant tumors, such as germ cell tumors, lymphomas, metastatic adenocarcinomas, hemangiopericytom as, and an anaplastic meningioma, In contrast, such activity was not d etected in benign tumors, including meningiomas, pituitary adenomas, h emangioblastomas and schwannomas, except for one hemangioblastoma that recurred four times acid displayed malignant features at the fourth r ecurrence. These findings suggest that telomerase activity can be an i ndex of malignant potential or malignancy itself in nonneuroepithelial brain tumors.