Hashimoto Naoya, Murakami Mamoru, Takahashi Yoshinobu, Fujimoto Masahito, Inazawa Johji, Mineura Katsuyoshi
Department of Neurosurgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Cancer. 2003 May 1;97(9):2254-61. doi: 10.1002/cncr.11322.
In oligodendroglial tumors, allelic losses on chromosome arms 1p and 19q are not only diagnostic molecular markers but also statistically significant predictors of both chemosensitivity and longer recurrence-free survival. In the current study, the authors attempted to analyze 21 patients genetically and clinically, with special emphasis on the correlation between genetic alterations and long-term therapeutic results.
The authors reviewed the clinical cases of 21 patients who had undergone surgery for oligodendroglial tumors (13 oligodendrogliomas, World Health Organization [WHO] Grade II; 3 anaplastic oligodendrogliomas, WHO Grade III; 3 oligoastrocytomas, WHO Grade II; and 2 anaplastic oligoastrocytomas, WHO Grade III). Genetic testing for 1p deletions was performed using fluorescence in situ hybridization, and testing for 1p, 17p, and 19q deletions was carried out by microsatellite analysis. Survival was analyzed with univariate and multivariate Cox regression models. In addition, a high-resolution deletion map of 1p, which led to the discovery of a new deleted region on 1p, was obtained.
Statistical analysis revealed that both loss of 1p and loss of 19q independently and significantly predicted overall survival. A high-resolution deletion map, which displayed unusually narrow deletions, revealed a new region of deletion between D1S513 and D1S458 (1p34.3-36.11).
One of the putative tumor suppressor loci exists more proximally than ever reported. Based on the observation that 1p and 19q deletions predicted survival, the authors suggest further use of diagnostic and prognostic genetic testing in the clinical setting.
在少突胶质细胞瘤中,1号染色体短臂(1p)和19号染色体长臂(19q)的等位基因缺失不仅是诊断性分子标志物,也是化疗敏感性和较长无复发生存期的统计学显著预测指标。在本研究中,作者试图对21例患者进行基因和临床分析,特别关注基因改变与长期治疗结果之间的相关性。
作者回顾了21例接受少突胶质细胞瘤手术患者的临床病例(13例少突胶质细胞瘤,世界卫生组织[WHO]二级;3例间变性少突胶质细胞瘤,WHO三级;3例少突星形细胞瘤,WHO二级;2例间变性少突星形细胞瘤,WHO三级)。使用荧光原位杂交技术进行1p缺失的基因检测,通过微卫星分析进行1p、17p和19q缺失检测。采用单因素和多因素Cox回归模型分析生存情况。此外,还获得了1p的高分辨率缺失图谱,该图谱导致在1p上发现了一个新的缺失区域。
统计分析显示,1p缺失和19q缺失均独立且显著地预测总生存期。一张显示异常狭窄缺失的高分辨率缺失图谱,揭示了D1S513和D1S458之间(1p34.3 - 36.11)的一个新缺失区域。
一个假定的肿瘤抑制基因座比以往报道的位置更靠近端粒。基于1p和19q缺失可预测生存的观察结果,作者建议在临床环境中进一步使用诊断和预后基因检测。