EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma
EWSR1-CREB1 is the predominant gene fusion in angiomatoid fibrous histiocytoma
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DOI：
10.1002/gcc.20491
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发表时间：
2007-12-01
影响因子：
3.7
通讯作者：
Ladanyi, Marc
中科院分区：
文献类型：
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作者：
Antonescu, Cristina R.;Dal Cin, Paola;Ladanyi, Marc
血管瘤样纤维组织细胞瘤（AFH）的分子标志尚未明确，迄今为止仅报告了6例具有特定基因融合的病例，包括FUS-ATFI或EWSRI-ATFI。为了解决这个问题，我们研究了FUS-ATFI，EWSRI-ATFI和高度相关的EWSRI-CREBI融合在一组9个AFH中的存在。所有病例均进行EWSRI-ATFI和EWSRI-CREBI的RT-PCR。在大多数情况下进行了EWSRI和FUS重排的FISH。在三种肿瘤中进行转录谱分析，并将其基因表达与表达EWSRI-ATFI或EWSRI-CREBI融合的五种透明细胞肉瘤进行比较。通过RT-PCR，9个肿瘤中有8个显示EWSRI-CREBI融合的存在，而1个具有EWSRI-ATFI转录物。FISH显示EWSRI重排的证据，在七个八例。在一个肿瘤中进行的核型分析显示t（2;22）（q33;q12）。在AFH肿瘤中注意到TFE 3的高转录水平，而在体细胞透明细胞肉瘤中注意到参与黑素生成的基因如MITF GP 100和MET的过表达。我们首次报道了AFH中EWSRI-CREBI的存在，这似乎是该肿瘤中最常见的基因融合。EWSR/-CREBI是最近在胃肠道透明细胞肉瘤中描述的一种新的易位。在一些AFH病例中发现的EWSRI-ATFI是软组织透明细胞肉瘤中最常见的遗传异常。因此，在两种不同的肉瘤中发现了涉及ATFI和CREBI的相同融合，这可能能够转化两种不同类型的间充质前体细胞，而不像大多数其他肉瘤基因融合。(c)2007 Wiley-Liss，Inc.
The molecular hallmark of angionnatoid fibrous histiocytoma (AFH) is not well defined, with only six cases with specific gene fusions reported to date, consisting of either FUS-ATFI or EWSRI-ATFI. To address this, we investigated the presence of FUS-ATFI, EWSRI-ATFI, and the highly related EWSRI-CREBI fusion in a group of nine AFHs. All cases were subjected to RT-PCR for EWSRI-ATFI and EWSRI-CREBI. FISH for EWSRI and FUS rearrangements was performed in most cases. Transcriptional profiling was performed in three tumors and their gene expression was compared to five clear cell sarcomas expressing either the EWSRI-ATFI or EWSRI-CREBI fusion. By RT-PCR, eight out of nine tumors showed the presence of the EWSRI-CREBI fusion, while one had an EWSRI-ATFI transcript. FISH showed evidence of EWSRI rearrangement in seven out of eight cases. Karyotypic analysis performed in one tumor showed a t(2;22)(q33;q12). High transcript levels were noted for TFE3 in AFH tumors, while overexpression of genes involved in melanogenesis, such as MITF GP100, and MET was noted in somatic clear cell sarcomas. We report for the first time the presence of EWSRI-CREBI in AFH, which now appears to be the most frequent gene fusion in this tumor. EWSR/-CREBI is a novel translocation recently described in clear cell sarcoma of the GI tract. EWSRI-ATFI, identified in some AFH cases, is the most common genetic abnormality in soft tissue clear cell sarcoma. Thus, identical fusions involving ATFI and CREBI are found in two distinct sarcomas, which may be able to transform two different types of mesenchymal precursor cells, unlike most other sarcoma gene fusions. (c) 2007 Wiley-Liss, Inc.