Raza-Egilmez S Z, Jani-Sait S N, Grossi M, Higgins M J, Shows T B, Aplan P D
Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Cancer Res. 1998 Oct 1;58(19):4269-73.
A novel chromosomal translocation, t(2;11)(q31;p15), was identified in a patient with therapy-related acute myelogenous leukemia (t-AML). Fluorescence in situ hybridization experiments mapped the breakpoint near NUP98; Southern blot analysis demonstrated that the nucleoporin gene NUP98 was disrupted by this translocation. We used rapid amplification of cDNA ends to identify a chimeric mRNA. An in-frame, chimeric mRNA that fused NUP98 sequences to the homeobox gene HOXD13 was cloned; the predicted fusion protein contains both the GLFG repeats from NUP98 as well as the homeodomain from HOXD13. The NUP98-HOXD13 fusion is structurally similar to the NUP98-HOXA9 fusion previously identified in patients with AML, leading to the speculation that NUP98-homeobox gene fusions may be oncogenic. Moreover, this report, along with a recent study that demonstrated NUP98-DDX10 fusions in patients with t-AML, raises the possibility that NUP98 may be a previously unsuspected target for chromosomal translocations in patients with t-AML.
在一名治疗相关的急性髓性白血病（t-AML）患者中，鉴定出一种新的染色体易位，即t(2;11)(q31;p15)。荧光原位杂交实验将断点定位在NUP98附近；Southern印迹分析表明，核孔蛋白基因NUP98因这种易位而被破坏。我们使用cDNA末端快速扩增技术来鉴定嵌合mRNA。克隆了一个将NUP98序列与同源框基因HOXD13融合的读框内嵌合mRNA；预测的融合蛋白既包含来自NUP98的GLFG重复序列，也包含来自HOXD13的同源结构域。NUP98-HOXD13融合在结构上与先前在AML患者中鉴定出的NUP98-HOXA9融合相似，这引发了NUP98-同源框基因融合可能具有致癌性的推测。此外，本报告以及最近一项在t-AML患者中发现NUP98-DDX10融合的研究，增加了NUP98可能是t-AML患者中先前未被怀疑的染色体易位靶点的可能性。
