Cerebral Tumour Research Group, Hormones and Cancer Unit, Kolling Institute of Medical Research, New South Wales, Australia.
J Neuropathol Exp Neurol. 2010 Jul;69(7):729-36. doi: 10.1097/NEN.0b013e3181e576cf.
Patients with glioblastoma (GBM) have variable clinical courses, but the factors that underlie this heterogeneity are not understood. To determine whether the presence of the telomerase-independent alternative lengthening of telomeres (ALTs) mechanism is a significant prognostic factor for survival, we performed a retrospective analysis of 573 GBM patients. The presence of ALT was identified in paraffin sections using a combination of immunofluorescence for promyelocytic leukemia body and telomere fluorescence in situ hybridization. Alternative lengthening of telomere was present in 15% of the GBM patients. Patients with ALT had longer survival that was independent of age, surgery, and other treatments. Mutations in isocitrate dehydrogenase (IDH1mut) 1 frequently accompanied ALT, and in the presence of both molecular events, there was significantly longer overall survival. These data suggest that most ALT+ tumors may be less aggressive proneural GBMs, and the better prognosis may relate to the set of genetic changes associated with this tumor subtype. Despite improved overall survival of patients treated with the addition of chemotherapy to radiotherapy and surgery, ALT and chemotherapy independently provided a survival advantage, but these factors were not found to be additive. These results suggest a critical need for developing new therapies to target these specific GBM subtypes.
胶质母细胞瘤（GBM）患者的临床病程存在差异，但导致这种异质性的因素尚不清楚。为了确定端粒酶非依赖性端粒延长的替代机制（ALT）的存在是否是生存的重要预后因素，我们对 573 例 GBM 患者进行了回顾性分析。使用早幼粒细胞白血病体的免疫荧光和端粒荧光原位杂交的组合，在石蜡切片中鉴定 ALT 的存在。15%的 GBM 患者存在 ALT。ALT 患者的生存时间更长，且与年龄、手术和其他治疗无关。异柠檬酸脱氢酶（IDH1mut）1 的突变常伴随着 ALT，并且在存在这两种分子事件的情况下，总生存期显著延长。这些数据表明，大多数 ALT+肿瘤可能是侵袭性较弱的成神经细胞瘤，较好的预后可能与与这种肿瘤亚型相关的一系列遗传变化有关。尽管接受放疗和手术加化疗治疗的患者的总体生存率有所提高，但 ALT 和化疗独立提供了生存优势，但这些因素并未发现具有加性。这些结果表明迫切需要开发针对这些特定 GBM 亚型的新疗法。
