Molecular markers of prognosis in Astrocytic tumors
Molecular markers of prognosis in Astrocytic tumors
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DOI：
10.1002/cncr.10544
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发表时间：
2002-05-15
期刊：
影响因子：
6.2
通讯作者：
McLendon, RE
中科院分区：
文献类型：
--
作者：
Rasheed, A;Herndon, JE;McLendon, RE
背景星形细胞瘤是一种原发性脑肿瘤，每年影响2万美国人。迄今为止，只有年龄和组织学分级作为生存的独立预测因素。现在越来越多的兴趣在使用的分子标记物作为客观标准，建立诊断和分级。该研究评估了63名男性和37名女性的新鲜速冻胶质瘤中的人类胶质瘤肿瘤抑制基因和相关位点，中位年龄为42岁，包括19例低级别星形细胞瘤。选择肿瘤样本，以便在该系列中代表来自年轻和老年患者的胶质母细胞瘤的数量大致相等。抑制基因和遗传位点的评价方法包括杂合性缺失（洛）分析、多重聚合酶链反应分析和基因测序。低级别星形细胞瘤的分子异常最少。9 p和/或CDKN 2A缺失的洛在胶质母细胞瘤中更常见（P < 0.001），17 p/TP 53突变的洛在间变性星形细胞瘤中更常见（AAs; P = 0.112），10 q/PTEN突变的洛频率在胶质母细胞瘤和AAs中相似（p < 0.001）。p16缺失（P = 0.031）、9 p洛（P = 0.016）或10 q洛缺失（P = 0.0007）与患者生存率显著相关。17 p位点洛缺失和PTEN突变的存在与生存率有一定的相关性。尽管TP 53突变在年轻胶质母细胞瘤患者中更常见，但在调整年龄后对生存率无统计学显著影响（P = 0.62）。在所有多变量模型中，年龄和年级是生存的唯一重要预测因素或几乎是生存的重要预测因素。结论。结果表明，尽管没有这些异常是无预后的，但9 p和p16缺失的洛可能被证明是高级别胶质瘤患者死亡诊断的客观标准。(C)2002年美国癌症协会。
BACKGROUND. Astrocytoma is a primary brain tumor that affects 20,000 Americans each year. To date, only age and histologic grade stand Out as independent predictors of survival. There is now increased interest hi the use of molecular markers as objective standards against which to establish diagnosis and grade.METHODS. The Study evaluated human glioma tumor suppressor genes and associated loci in fresh snap-frozen gliomas from 63 males and 37 females, with a median age of 42 years, including 19 low-grade astrocytomas. The tumor samples were selected so that about equal numbers of glioblastomas from younger and older patients were represented In the Series. Methods for suppressor gene and genetic loci evaluation included loss of heterozygosity (LOH) analysis, multiplex polymerase chain reaction analysis, and gene sequencing.RESULTS. Low-grade astrocytomas had the least number of molecular abnormalities. LOH on 9p and/or CDKN2A deletion occurred more often in glioblastomas (P < 0.001), LOH on 17p/TP53 mutations occurred more frequently in anaplastic astrocytomas (AAs; P = 0.112), and LOH on 10q/PTEN mutation frequency was similar in glioblastomas and AAs (p < 0.001). Poorer survival was associated significantly with the occurrence of either deletion of p16 (P = 0.031), LOH on 9p (P = 0.016), or LOH on 10q (P = 0.0007). The absence of LOH on 17p and the presence of PTEN mutation were associated marginally with survival. Even though TP53 mutations were more frequent among younger patients with glioblastoma, they had no statistically significant effect on survival after adjustment for age (P = 0.62). In all multivariate models, age and grade were the only significant predictors of survival or were nearly significant predictors of survival.CONCLUSIONS. The results suggest that LOH on 9p and p16 deletions may prove to he objective standards for die diagnosis of patients with high-grade gliomas, although the absence of these abnormalities is nonprognostic. (C) 2002 American Cancer Society.