Comprehensive genetic and epigenetic analysis of sporadic meningioma for macro-mutations on 22q and micro-mutations within the NF2 locus.
Comprehensive genetic and epigenetic analysis of sporadic meningioma for macro-mutations on 22q and micro-mutations within the NF2 locus.
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DOI：
10.1186/1471-2164-8-16
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发表时间：
2007-01-12
期刊：
影响因子：
4.4
通讯作者：
Dumanski JP
中科院分区：
文献类型：
--
作者：
Hansson CM;Buckley PG;Grigelioniene G;Piotrowski A;Hellström AR;Mantripragada K;Jarbo C;Mathiesen T;Dumanski JP
脑膜瘤是最常见的颅内肿瘤，代表一组临床和组织病理学异质性的肿瘤。 2 型神经纤维瘤病 (NF2) 肿瘤抑制基因是唯一已知经常参与脑膜瘤早期发展的基因。本研究的目的是确定导致这些肿瘤发生的遗传和/或表观遗传因素。使用阵列 CGH 分析大量散发性脑膜瘤是否存在 22q 宏突变，以识别携带不包含 NF2 的基因剂量畸变的肿瘤。还对 NF2 基因座的编码和保守非编码序列内的点突变进行了全面研究。此外，还彻底分析了 NF2 启动子区域内的 CpG 甲基化。 22 单体是主要发现，在 47% 的脑膜瘤中检测到。 13% 的肿瘤含有间质/末端缺失和增益，单独或组合存在。我们在 NF2 基因座之外定义了至少两个最小重叠区域，这些区域足够小（~550 kb 和~250 kb），以允许分析有限数量的候选基因。在 36% 的脑膜瘤中检测到 NF2 基因双等位基因失活。在 22 例单体性肿瘤中，35%（49 个肿瘤中的 17 个）未发现额外的 NF2 突变。此外，大多数具有间质/末端缺失的肿瘤（12 个中有 9 个）没有任何可检测到的 NF2 突变。仅在一份肿瘤样本中的单个 CpG 位点上发现了 NF2 启动子区域内的甲基化。我们证实了之前的发现，即不同组织病理学亚型之间突变频率存在显着差异。与脑膜上皮肿瘤 (18%) 相比，成纤维细胞肿瘤 (52%) 中双等位基因 NF2 失活的频率更高。 22q 上宏突变的存在也显示出成纤维细胞 (86%) 和脑膜皮细胞 (39%) 亚型之间的显着差异。因此，与成纤维细胞形式相反，NF2 失活通常与 22q 上存在的宏突变相结合，对于脑膜上皮亚型的发育可能不那么重要。对分布在启动子区域 750 bp 内的 40 个 CpG 位点的分析表明，NF2 启动子甲基化在脑膜瘤的发展中不起主要作用。
Meningiomas are the most common intracranial neoplasias, representing a clinically and histopathologically heterogeneous group of tumors. The neurofibromatosis type 2 (NF2) tumor suppressor is the only gene known to be frequently involved in early development of meningiomas. The objective of this study was to identify genetic and/or epigenetic factors contributing to the development of these tumors. A large set of sporadic meningiomas were analyzed for presence of 22q macro-mutations using array-CGH in order to identify tumors carrying gene dosage aberrations not encompassing NF2. The NF2 locus was also comprehensively studied for point mutations within coding and conserved non-coding sequences. Furthermore, CpG methylation within the NF2 promoter region was thoroughly analyzed. Monosomy 22 was the predominant finding, detected in 47% of meningiomas. Thirteen percent of the tumors contained interstitial/terminal deletions and gains, present singly or in combinations. We defined at least two minimal overlapping regions outside the NF2 locus that are small enough (~550 kb and ~250 kb) to allow analysis of a limited number of candidate genes. Bialleinactivationo the NF2 gne was detected in 36% of meningiomas. Among the monosomy 22 cases, no additional NF2 mutations could be identified in 35% (17 out of 49) of tumors. Furthermore, the majority of tumors (9 out of 12) with interstitial/terminal deletions did not have any detectable NF2 mutations. Methylation within the NF2 promoter region was only identified at a single CpG site in one tumor sample. We confirmed previous findings of pronounced differences in mutation frequency between different histopathological subtypes. There is a higher frequency of biallelic NF2 inactivation in fibroblastic (52%) compared to meningothelial (18%) tumors. The presence of macro-mutations on 22q also shows marked differences between fibroblastic (86%) and meningothelial (39%) subtypes. Thus, inactivation of NF2, often combined with the presence of macro-mutation on 22q, is likely not as important for the development of the meningothelial subtype, as opposed to the fibroblastic form. Analysis of 40 CpG sites distributed within 750 bp of the promoter region suggests that NF2 promoter methylation does not play a major role in meningioma development.
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影响因子：
2.7
作者：
Colella, S;Shen, L;Krahe, R
通讯作者：
Krahe, R
影响因子：
12.7
作者：
Bello, MJ;Amiñoso, C;Rey, JA
通讯作者：
Rey, JA
影响因子：
4
作者：
EVANS, DGR;HUSON, SM;HARRIS, R
通讯作者：
HARRIS, R
DOI：
10.1093/jnen/60.6.628
发表时间：
2001-06-01
影响因子：
3.2
作者：
Cai, DX;Banerjee, R;Perry, A
通讯作者：
Perry, A
影响因子：
4
作者：
Evans, DGR;Watson, C;Baser, ME
通讯作者：
Baser, ME