A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma
A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma
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DOI：
10.1038/ng0298-184
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发表时间：
1998-02-01
期刊：
影响因子：
30.8
通讯作者：
Sorensen, PHB
中科院分区：
文献类型：
--
作者：
Knezevich, SR;McFadden, DE;Sorensen, PHB
先天性（或婴儿）纤维肉瘤（CFS）是一种恶性肿瘤的成纤维细胞，发生在患者年龄在两岁或以下。CFS在人类肉瘤中是独特的，因为它具有良好的预后和非常低的转移率（1，2）。CFS在组织学上与成人型纤维肉瘤（ATFS）相同;然而，ATFS是成人和年龄较大儿童的侵袭性恶性肿瘤，预后不良（3）。我们报告了一种新的复发性t（12;15）（p13;q25）重排CFS，可能是这种肿瘤独特的生物学特性的基础。通过克隆染色体断裂点，我们发现重排融合了来自12 p13的ETV 6（也称为TEL）基因与15 q25 NTRK 3神经营养因子-3受体基因（也称为TRKC）。mRNA的分析揭示了ETV 6-NTRK 3嵌合体转录物在所分析的所有三种CFS肿瘤中的表达。这些在ATFS或婴儿纤维瘤病（IFB）中未检测到，IFB是一种与CFS发生在相同年龄组的组织学相似但良性的成纤维细胞增殖。ETV 6-NTRK 3融合转录物编码融合到NTRK 3的蛋白酪氨酸激酶（PTK）结构域的ETV 6的螺旋-环-螺旋（HLH）蛋白二聚化结构域。我们的研究表明，嵌合PTK在CFS中表达，这可能有助于通过NTRK 3信号转导通路的失调而导致肿瘤发生。此外，ETV 6-NTRK 3基因融合体为CFS提供了潜在的诊断标志物。
Congenital (or infantile) fibrosarcoma (CFS) is a malignant tumour of fibroblasts that occurs in patients aged two years or younger. CFS is unique among human sarcomas in that it has an excellent prognosis and very low metastatic rate(1,2). CFS is histologically identical to adult-type fibrosarcoma (ATFS); however, ATFS is an aggressive malignancy of adults and older children that has a poor prognosis(3). We report a novel recurrent t(12;15)(p13;q25) rearrangement in CFS that may underlie the distinctive biological properties of this tumour. By cloning the chromosome breakpoints, we show that the rearrangement fuses the ETV6 (also known as TEL) gene from 12p13 with the 15q25 NTRK3 neurotrophin-3 receptor gene (also known as TRKC). Analysis of mRNA revealed the expression of ETV6-NTRK3 chimaeric transcripts in all three CFS tumours analysed. These were not detected in ATFS or infantile fibromatosis (IFB), a histologically similar but benign fibroblastic proliferation occurring in the same age-group as CFS. ETV6-NTRK3 fusion transcripts encode the helix-loop-helix (HLH) protein dimerization domain of ETV6 fused to the protein tyrosine kinase (PTK) domain of NTRK3. Our studies indicate that a chimaeric PTK is expressed in CFS and this may contribute to oncogenesis by dysregulation of NTRK3 signal transduction pathways. Moreover, ETV6-NTRK3 gene fusions provide a potential diagnostic marker for CFS.