Inactivation patterns of NF2 and DAL-1/4.1B (EPB41L3) in sporadic meningioma
Inactivation patterns of NF2 and DAL-1/4.1B (EPB41L3) in sporadic meningioma
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DOI：
10.1016/j.cancergencyto.2005.04.003
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发表时间：
2005-10-15
影响因子：
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通讯作者：
MacCollin, M
中科院分区：
文献类型：
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作者：
Nunes, F;Shen, YP;MacCollin, M
脑膜瘤肿瘤发生和肿瘤进展的分子基础尚不完全清楚。神经纤维瘤病 2 (NF2) 位点在 50-60% 的散发性脑膜瘤中失活，但 NF2 位点未失活的散发性脑膜瘤的遗传基础仍不清楚。具体而言，关于肿瘤抑制基因 DAL-1/4.1B 的作用存在相互矛盾的数据。使用微卫星标记，我们研究了 63 个散发性脑膜瘤，以确定 NF2 和 DAL-1/1.B 基因座的杂合性丢失 (LOH)。对其中 52 个肿瘤进行阵列比较基因组杂交分析，以确定 18 号和 22 号染色体上的拷贝数变化。62 个信息性肿瘤中的 41 个显示 NF2 基因座处的 LOH (66%)，而 62 个信息性肿瘤中只有 12 个 (19%) 显示 DAL-1/4.1B 的 LOH。 12 个具有 DAL-1/4.1B LOH 的肿瘤中有 11 个 (92%) 也具有 NF2 LOH。 18 号和 22 号染色体的单体性或大缺失是这些肿瘤中 LOH 的主要机制。这些研究表明，散发性脑膜瘤中 DAL-1/4.1B 基因座的发生率比之前报道的要少，并且表明它是一个进展而非起始基因座。此外，我们发现大多数脑膜瘤在 NF2 和 DAL-114.1B 基因座上形成单体而不是等二体，这是 LOH 的机制。 (c) 2005 Elsevier Inc. 保留所有权利。
The molecular basis of tumorigenesis and tumor progression in meningiomas is not fully understood. The neurofibromatosis 2 (NF2) locus is inactivated in 50-60% of sporadic meningiomas, but the genetic basis of sporadic meningiomas not inactivated at the NF2 locus remains unclear. Specifically, there is conflicting data regarding the role of the tumor suppressor gene DAL-1/4.1B. Using microsatellite markers, we studied 63 sporadic meningiomas to determine loss of heterozygosity (LOH) at the NF2 and DAL-1/1.B loci. Array comparative genomic hybridization analysis of 52 of these tumors was performed to determine copy number changes on chromosomes 18 and 22. Forty-one of 62 informative tumors showed LOH at the NF2 locus (66%) while only 12 of 62 informative tumors (19%) showed LOH of DAL-1/4.1B. Eleven of 12 (92%) tumors with DAL-1/4.1B LOH also had NF2 LOH. Monosomy or large deletions of chromosomes 18 and 22 were the main mechanism for LOH in these tumors. These studies implicate the DAL-1/4.1B locus in sporadic meningiomas less commonly than reported previously, and suggest that it is a progression rather than an initiation locus. Furthermore, we found the majority of meningiomas developed monosomy rather than isodisomy at the NF2 and DAL-114.1B loci as the mechanism for LOH. (c) 2005 Elsevier Inc. All rights reserved.