非典型脑膜瘤患者的癌基因低水平扩增与年龄呈负相关。

Low-level amplification of oncogenes correlates inversely with age for patients with nontypical meningiomas.

机构信息

Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA.

出版信息

World Neurosurg. 2013 Feb;79(2):313-9.e1-10. doi: 10.1016/j.wneu.2011.08.023. Epub 2011 Nov 7.

DOI:10.1016/j.wneu.2011.08.023

PMID:22120298

Abstract

BACKGROUND

This study sought to identify genes in nontypical meningiomas with gains in copy number (CN) that correlate with earlier age of onset, an indicator of aggressiveness.

METHODS

Among 94 adult patients, 91 had 105 meningiomas that were histologically confirmed. World Health Organization grades I (typical), II (atypical), and III (anaplastic) were assigned to tumors in 76, 14, and 1 patient, respectively. Brain invasion indicated that two World Health Organization grade I meningiomas were biologically atypical. DNA from 15 invasive/atypical/anaplastic meningiomas and commercial normal DNA were analyzed with multiplex ligation dependent probe amplification. The CN ratios (fold differences from normal) for 78 genes were determined. The CN ratio was defined as [tumor CN]/[normal CN] for each gene to normalize results.

RESULTS

Characteristic gene losses (CN ratio < 0.75) occurred in >50% of the invasive/atypical/anaplastic meningiomas at 22q11, 1p34.2, and 1p22.1 loci. Gains (CN ratio ≥ 2.0) occurred in each tumor for 2 or more of 19 genes. Each of the 19 genes' CN ratio was ≥ 2.0 in multiple tumors, and their collective sums (up to 49.1) correlated inversely with age (r = -0.72), minus an outlier. In patients ≤ 55 versus >55 years, 5 genes (BIRC2, BRAF, MET, NRAS, and PIK3CA) individually exhibited significantly higher CN ratios (P < 0.05) or a trend for them (P < 0.09), with corrections for multiple comparisons, and their sums correlated inversely with age (r = -0.74).

CONCLUSIONS

Low levels of amplification for selected oncogenes in invasive/atypical/anaplastic meningiomas were higher in younger adults, with the CN gains potentially underlying biological aggressiveness associated with early tumor development.

摘要

背景

本研究旨在鉴定非典型脑膜瘤中与发病年龄较早相关的拷贝数（CN）增益的基因，这是侵袭性的一个指标。

方法

在 94 名成年患者中，91 名患者有 105 个经组织学证实的脑膜瘤。世界卫生组织（WHO）I 级（典型）、II 级（非典型）和 III 级（间变）分别分配给 76 例、14 例和 1 例肿瘤。脑侵犯表明，两个 WHO 分级 I 级脑膜瘤在生物学上是非典型的。用多重连接依赖性探针扩增分析了 15 例侵袭性/非典型/间变性脑膜瘤和商业正常 DNA 的 DNA。确定了 78 个基因的 CN 比（与正常相比的倍数差异）。CN 比定义为每个基因的[肿瘤 CN]/[正常 CN]，以归一化结果。

结果

超过 50%的侵袭性/非典型/间变性脑膜瘤在 22q11、1p34.2 和 1p22.1 位点发生特征性基因缺失（CN 比<0.75）。每个肿瘤均有 2 个或更多的 19 个基因发生增益（CN 比≥2.0）。19 个基因中的每一个基因的 CN 比都在多个肿瘤中≥2.0，它们的总和（高达 49.1）与年龄呈负相关（r=-0.72），减去一个异常值。在≤55 岁与>55 岁的患者中，5 个基因（BIRC2、BRAF、MET、NRAS 和 PIK3CA）的 CN 比单独显著升高（P<0.05）或呈升高趋势（P<0.09），在进行多次比较校正后，它们的总和与年龄呈负相关（r=-0.74）。