Mutations in Rb1 pathway-related genes are associated with poor prognosis in anaplastic astrocytomas.
Mutations in Rb1 pathway-related genes are associated with poor prognosis in anaplastic astrocytomas.
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DOI：
10.1038/sj.bjc.6602661
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发表时间：
2005-07-11
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
间变性星形细胞瘤（AA，WHO III级）是仅次于胶质母细胞瘤的最常见和最恶性的成人CNS肿瘤。由于AA患者的生存率差异显著，并且没有已知有用的预后或治疗反应指标，因此本研究的主要目的是检查AA中发现的已知遗传异常的知识是否具有任何临床价值。37个仔细取样的AA的存活数据与已知参与星形细胞肿瘤发展的9个基因的状态的详细分析结果相关。这些基因包括编码p53途径中的蛋白质的三个基因（TP53、p14ARF和MDM2）、编码Rb 1途径中的四个基因（CDKN2A、CDKN2B、RB1和CDK4）以及编码PTEN和EGFR的基因。我们发现，三种肿瘤抑制基因CDKN2A、CDKN2B和RB1中任何一种的两种野生型拷贝的丢失或CDK4的基因扩增，破坏Rb1通路，与较短的生存期相关（P=0.009）。这种关联在多变量分析中是一致的，包括年龄调整（P=0.013）。研究结果表明，Rb1通路成分的基因编码的分析提供了额外的预后信息，在接受常规治疗的AA患者。
Anaplastic astrocytoma (AA, WHO grade III) is, second to Glioblastoma, the most common and most malignant type of adult CNS tumour. Since survival for patients with AA varies markedly and there are no known useful prognostic or therapy response indicators, the primary purpose of this study was to examine whether knowledge of the known genetic abnormalities found in AA had any clinical value. The survival data on 37 carefully sampled AA was correlated with the results of a detailed analysis of the status of nine genes known to be involved in the development of astrocytic tumours. These included three genes coding for proteins in the p53 pathway (TP53, p14ARF and MDM2), four in the Rb1 pathway (CDKN2A, CDKN2B, RB1 and CDK4) and PTEN and EGFR. We found that loss of both wild-type copies of any of the three tumour suppressor genes CDKN2A, CDKN2B and RB1 or gene amplification of CDK4, disrupting the Rb1 pathway, were associated with shorter survival (P=0.009). This association was consistent in multivariate analysis, including adjustment for age (P=0.013). The findings suggest that analysis of the genes coding for Rb1 pathway components provides additional prognostic information in AA patients receiving conventional therapy.
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DOI：
10.1097/00005072-199911000-00007
发表时间：
1999-11-01
影响因子：
3.2
作者：
Schmidt, EE;Ichimura, K;Collins, VP
通讯作者：
Collins, VP
DOI：
10.1097/00005072-198805000-00001
发表时间：
1988-05-01
影响因子：
3.2
作者：
BIGNER, SH;BURGER, PC;BIGNER, DD
通讯作者：
BIGNER, DD
影响因子：
--
作者：
Lin, CL;Lieu, AS;Hwang, SL
通讯作者：
Hwang, SL
影响因子：
6.2
作者：
Rasheed, A;Herndon, JE;McLendon, RE
通讯作者：
McLendon, RE
影响因子：
6.4
作者：
Watanabe, K;Sato, K;Ohgaki, H
通讯作者：
Ohgaki, H