Prognostic impact of molecular markers in a series of 220 primary glioblastomas
Prognostic impact of molecular markers in a series of 220 primary glioblastomas
复制标题
DOI：
10.1002/cncr.21819
复制
发表时间：
2006-05-15
期刊：
影响因子：
6.2
通讯作者：
Sanson, M
中科院分区：
文献类型：
--
作者：
Houillier, C;Lejeune, J;Sanson, M
背景。与少突胶质细胞瘤相反，胶质母细胞瘤的预后分子预测因子尚未被一致发现。然而，遗传学研究表明，胶质母细胞瘤由几种遗传亚型组成，并提出了分子改变可以预测生存的可能性。在220例原发性胶质母细胞瘤中，研究了染色体1p， 9p, 10q， 19q上的杂合性缺失（LOH），表皮生长因子受体（EGFR）， CDK4和MDM2（小鼠双分钟）扩增，CDKN2A （INK4A/ARF）纯合缺失，p53表达。然后将分子改变相互关联以确定不同的分子途径，并与临床参数和疾病病程相关联以确定预后标志物。EGFR扩增与LOH10q、LOH9p和INK4A/ARF缺失、LOH1p和LOH19q、MDM2和CDK4扩增之间存在非随机关联，而p53表达与EGFR扩增、LOH9p /INK4A/ARF纯合缺失、MDM2和CDK4扩增之间存在相互排斥。年龄（P = 4.10(-5)）和运动状态（P = 0.003）是预后的主要预测因素。相比之下，分子标记的影响有限：MDM2扩增在单因素和多因素分析中与预后差相关（P = 0.01）， EGFR扩增在多因素分析中与预后好相关（P = 0.02）。尽管遗传标记对预后的影响有限，但本文研究的遗传标记概述了胶质母细胞瘤发生过程中不同的分子途径，需要更广泛的分子筛选。
BACKGROUND. in contrast to oligodendrogliomas, molecular predictors of prognosis have not been consistently found in glioblastomas. However, genetic studies show that glioblastomas consist of several genetic subtypes and raise the possibility that molecular alterations could be predictive of survival.METHODS. A search for loss of heterozygosity (LOH) on chromosome 1p, 9p, 10q, 19q, EGFR (epidermal growth factor receptor), CDK4, and MDM2 (mouse double minute) amplifications, CDKN2A (INK4A/ARF) homozygous deletions, p53 expression, was performed in a series of 220 primary glioblastomas. The molecular alterations were then correlated with each other to identify distinct molecular pathways and with clinical parameters and the course of the disease to identify prognostic markers.RESULTS. Nonrandom associations were found between EGFR amplification and LOH10q, LOH9p, and INK4A/ARF deletion, LOH1p and LOH19q, and MDM2 and CDK4 amplification, whereas Mutual exclusions were found between p53 expression and EGFR amplification, LOH 9p/INK4A/ARF homozygous deletion, and MDM2 and CDK4 amplification. Age (P = 4.10(-5)) and performance status (P = .003) were the main predictors Of Outcome. In contrast, molecular markers were of limited impact: MDM2 amplification correlated with poor outcome on both univariate and multivariate analysis (P = .01) and EGFR amplification with good prognosis on multivariate analysis (P = .02).CONCLUSION. Despite their limited prognostic impact, the genetic markers investigated here outline distinct molecular pathways involved in glioblastoma tumorigenesis and warrant broader molecular screening.