A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia
A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia
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DOI：
10.1182/blood.v98.4.1264
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发表时间：
2001-08-15
期刊：
影响因子：
20.3
通讯作者：
Wainscoat, JS
中科院分区：
文献类型：
--
作者：
Jaju, RJ;Fidler, C;Wainscoat, JS
据报道，儿童急性髓系白血病 (AML) 中存在与 5q 缺失 del(5q) 相关的反复易位 t(5;11)(q35; p15.5)。我们报告了新发儿童 AML 中易位断点的克隆，其中含有神秘的 t(5;11)(q35;p15.5)。荧光原位杂交 (FISH) 分析表明，11p15.5 处的核孔蛋白基因 (NUP98) 被这种易位破坏。通过使用互补 DNA 末端的 3'-快速扩增 (3'-RACE) 聚合酶链式反应，我们鉴定了一种嵌合信使 RNA，它导致 NUP98 与新基因 NSD1 框内融合。 NSD1基因有2596个氨基酸残基，与鼠Nsd1有85%的同源性，且结构域结构保守。 NSD1基因经FISH定位于5q35并广泛表达。还通过逆转录酶-聚合酶链式反应检测到了互逆转录本 NSDI-NUP98。这是第一份新基因 NSD1 与人类恶性肿瘤有关的报告。
The recurrent translocation t(5;11)(q35; p15.5) associated with a 5q deletion, del(5q), has been reported in childhood acute myeloid leukemia (AML). We report the cloning of the translocation breakpoints in de novo childhood AML harboring a cryptic t(5;11)(q35;p15.5). Fluorescence in situ hybridization (FISH) analysis demonstrated that the nucleoporin gene (NUP98) at 11p15.5 was disrupted by this translocation. By using 3'-rapid amplification of complementary DNA ends (3'-RACE) polymerase chain reaction, we identified a chimeric messenger RNA that results in the in-frame fusion of NUP98 to a novel gene, NSD1. The NSD1 gene has 2596 amino acid residues and a 85% homology to the murine Nsd1 with the domain structure being conserved. The NSD1 gene was localized to 5q35 by FISH and is widely expressed. The reciprocal transcript, NSDI-NUP98, was also detected by reverse transcriptase-polymerase chain reaction. This is the first report in which the novel gene NSD1 has been implicated in human malignancy.