Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor
Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor
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DOI：
10.1002/gcc.10033
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发表时间：
2002-08-01
影响因子：
3.7
通讯作者：
Marynen, P
中科院分区：
文献类型：
--
作者：
Cools, J;Wlodarska, I;Marynen, P
ALK阳性间变性大细胞淋巴瘤（ALCL）已被认为是T/NuII-ALCL异质性组中的一种独特类型的淋巴瘤，而大多数ALK阳性ALCL（ALKomas）的特征是存在NPM-ALK融合蛋白，即t（2;5）（p23; q35），10-20%的ALK瘤含有ALK融合变体，包括ATIC-ALK、TFG-ALK、CLTC-ALK（以前称为CLTCL-ALK）、TMP 3-ALK和MSN-ALK。在炎性肌纤维母细胞瘤（IMT）中也检测到了TMP 3-ALK和TMP 4-ALK融合，这表明ALK基因的畸变并非仅与ALK阳性ALCL的发病机制相关。在这里，我们报告的分子研究结果，两个淋巴瘤的情况下，一个IMT的情况下，变异重排的ALK。我们的研究导致在ALCL病例中检测到CLTC-ALK融合，并鉴定出ALK的两种新型融合伴侣：ALO 17（KIAA 1618），一种功能未知的基因，在ALCL病例中与ALK融合，具有t（2;17）（p23;q25），和汽车，编码半胱氨酰-tRNA合成酶，在IMT病例中与ALK融合，具有t（2;11; 2）（p23; p15;问题31）。这些结果证实了ALK在IMT中的复发性参与，并进一步证明了ALK融合伴侣的多样性，同源二聚化能力是一个共同特征。(C)2002 Wiley-Liss，Inc.
ALK-positive anaplastic large-cell lymphoma (ALCL) has been recognized as a distinct type of lymphoma in the heterogeneous group of T/NuII-ALCL While most of the ALK-positive ALCL (ALKomas) are characterized by the presence of the NPM-ALK fusion protein, the product of the t(2;5)(p23;q35), 10-20% of ALKomas contain variant ALK fusions, including ATIC-ALK, TFG-ALK, CLTC-ALK (previously designated CLTCL-ALK), TMP3-ALK, and MSN-ALK. TMP3-ALK and TMP4-ALK fusions also have been detected in inflammatory myofibroblastic tumors (IMTs), making clear that aberrations of the ALK gene are not associated exclusively with the pathogenesis of ALK-positive ALCL. Here we report results of molecular studies on two lymphoma cases and one IMT case with variant rearrangements of ALK. Our study led to the detection of the CLTC-ALK fusion in an ALCL case and to the identification of two novel fusion partners of ALK: ALO17 (KIAA1618), a gene with unknown function, which was fused to ALK in an ALCL case with a t(2;17)(p23;q25), and CARS, encoding the cysteinyl-tRNA synthetase, which was fused to ALK in an IMT case with a t(2;11;2)(p23;p15;q31). These results confirm the recurrent involvement of ALK in IMT and further demonstrate the diversity of ALK fusion partners, with the ability to homodimerize as a common characteristic. (C) 2002 Wiley-Liss, Inc.