Labelle Y, Zucman J, Stenman G, Kindblom L G, Knight J, Turc-Carel C, Dockhorn-Dworniczak B, Mandahl N, Desmaze C, Peter M
Génétique des Tumeurs, Institut Curie, Paris, France.
Hum Mol Genet. 1995 Dec;4(12):2219-26. doi: 10.1093/hmg/4.12.2219.
A recurrent t(9;22) (q22;q12) chromosome translocation has been described in extraskeletal myxoid chondrosarcoma (EMC). Fluorescent in situ hybridization experiments performed on one EMC tumour indicated that the chromosome 22 breakpoint occurred in the EWS gene. Northern blot analysis revealed an aberrant EWS transcript which is cloned by a modified RT-PCR procedure. This transcript consists of an in-frame fusion of the 5' end of EWS to a previously unidentified gene, which was named TEC. This fusion transcript was detected in six of eight EMC studied, and three different junction types between the two genes were found. In all junction types, the putative translation product contained the amino-terminal transactivation domain of EWS linked to the entire TEC protein. Homology analysis showed that the predicted TEC protein contains a DNA-binding domain characteristic of nuclear receptors. The highest identity scores were observed with the NURR1 family of orphan nuclear receptors. These receptors are involved in the control of cell proliferation and differentiation by modulating the response to growth factors and retinoic acid. This work provides, after the PML/RAR alpha gene fusion, the second example of the oncogenic conversion of a nuclear receptor and the first example involving the orphan subfamily. Analysis of the disturbance induced by the EWS/TEc protein in the nuclear receptor network and their target genes may lead to new approaches for EMC treatment.
在骨外黏液样软骨肉瘤（EMC）中已发现一种复发性t(9;22) (q22;q12) 染色体易位。对一例EMC肿瘤进行的荧光原位杂交实验表明，22号染色体断点发生在EWS基因中。Northern印迹分析显示一种异常的EWS转录本，通过改良的逆转录聚合酶链反应（RT-PCR）程序对其进行克隆。该转录本由EWS 5'端与一个先前未鉴定的基因的读框内融合组成，该基因被命名为TEC。在研究的8例EMC中有6例检测到这种融合转录本，并且发现了两个基因之间的三种不同连接类型。在所有连接类型中，推定的翻译产物包含与整个TEC蛋白相连的EWS氨基末端反式激活结构域。同源性分析表明，预测的TEC蛋白含有核受体特有的DNA结合结构域。与孤儿核受体NURR1家族的同源性得分最高。这些受体通过调节对生长因子和视黄酸的反应参与细胞增殖和分化的控制。这项工作在PML/RARα基因融合之后，提供了核受体致癌转化的第二个例子以及涉及孤儿亚家族的第一个例子。分析EWS/TEC蛋白在核受体网络及其靶基因中引起的干扰可能会为EMC治疗带来新方法。
