グリオーマにおけるテロメレース活性およびテロメア長の臨床応用への検討

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Telomeres progressively shorten with age in somatic cells in culture and in vivo because DNA replication results in the loss of chromosome ends. Normal cells in vivo and in vitro have a limited lifespan, whereas tumor cells can often grow indefinitely. Telomerase, a ribonucleoprotein which extends shortened chromosomal ends is re-expressed in most tumors. However, there are only a few reports on telomere length and telomerase in intracranial tumors. Thus, we examined telomere length and telomerase activity in gliomas, and FISH analysis of telomeres interphase nuclei for its usefulness as tumor markers. In this study, the telomere restriction fragments and telomerase activity were studied in 50 patients with various grades of gliomas. Telomerase activity was frequently positive in glioblastomas (86%), and telomere lengths were similar or shorter, compared with those in normal tissues. Some cases were repeatedly examined and had the positive telomerase activity during a tumor progression. In one case, however, tumor cells initially were negative for the activity and become positive, accompanied with a significant TRF shortening. Unlike most malignant tumors, longer TRFs than those in normal tissues were observed in 35% of the samples. Most of them were of astrocytoma (Grade 3). Fluorescence in situ hybridization showed that cases with longer telomerase-negative, and shorter (telomere-positive) telomeres can be detected, suggesting that FISH analysis in interphases and paraffin sections are useful for clinical applications.