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

体细胞的端粒随着年龄的增长而逐渐缩短，这是由于DNA复制导致染色体末端的丢失。体内和体外的正常细胞寿命有限，而肿瘤细胞通常可以无限生长。端粒酶是一种延长缩短的染色体末端的核糖核蛋白，在大多数肿瘤中重新表达。然而，关于端粒长度和端粒酶在颅内肿瘤中的作用的报道很少。因此，我们检测了胶质瘤中的端粒长度和端粒酶活性，并对端粒间期核进行了FISH分析，以确定其作为肿瘤标志物的用途。本研究对50例不同级别胶质瘤患者的端粒限制性片段和端粒酶活性进行了研究。端粒酶活性在胶质母细胞瘤中经常呈阳性（86%），端粒长度与正常组织相似或更短。一些病例在肿瘤进展过程中反复检查端粒酶活性呈阳性。然而，在一个病例中，肿瘤细胞最初的活性是阴性的，然后变成阳性的，伴随着显著的TRF缩短。与大多数恶性肿瘤不同，在35%的样本中观察到比正常组织更长的TRFs。多数为星形细胞瘤（3级）。荧光原位杂交显示，可以检测到端粒酶阴性较长和端粒阳性较短的病例，表明间期和石蜡切片的FISH分析具有临床应用价值。

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.