TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors
TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors
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DOI：
10.1016/s0002-9440(10)64550-6
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发表时间：
2000-08-01
影响因子：
6
通讯作者：
Fletcher, JA
中科院分区：
文献类型：
--
作者：
Lawrence, B;Perez-Atayde, A;Fletcher, JA
炎性肌纤维母细胞瘤（IMTs）是一种肿瘤间充质增生，主要由淋巴细胞和浆细胞组成炎性浸润。一些IMTs的肌成纤维细胞含有涉及ALK受体酪氨酸激酶位点区域（染色体带2p23）的染色体重排。alk通常只在神经组织中表达，但在2p23重排的IMT细胞中却显著表达。我们现在报道了一种复发性的致癌机制，在imt中，原肌球蛋白（TPM） n端卷曲结构域与ALK融合。c末端激酶结构域。我们克隆了两个ALK融合基因，TPM4-ALK和TPM3-ALK，它们编码类似于95-kd融合癌蛋白，其特征是组成激酶活性和酪氨酸磷酸化。在其他IMTs中，免疫组织化学和分子相关性暗示非tpm ALK癌蛋白主要是细胞质或核，可能取决于ALK融合伙伴的亚细胞定位。值得注意的是，最近在间变性淋巴瘤中报道了TPM3-ALK癌基因，因此TPM3-ALK是第一个已知的在体内转化人间充质细胞和淋巴细胞谱系的融合癌基因。
Inflammatory myofibroblastic tumors (IMTs) are neoplastic mesenchymal proliferations featuring an inflammatory infiltrate composed primarily of lymphocytes and plasma cells. The myofibroblastic cells in some IMTs contain chromosomal rearrangements involving the ALK receptor tyrosine-kinase locus region (chromosome band 2p23). ALK-which is normally restricted in its expression to neural tissues-is expressed strikingly in the IMT cells with 2p23 rearrangements. We now report a recurrent oncogenic mechanism, in IMTs, in which tropomyosin (TPM) N-terminal coiled-coil domains are fused to the ALK. C-terminal kinase domain. We have cloned two ALK fusion genes, TPM4-ALK and TPM3-ALK, which encode similar to 95-kd fusion oncoproteins characterized by constitutive kinase activity and tyrosylphosphorylation. Immunohistochemical and molecular correlations, in other IMTs, implicate non-TPM ALK oncoproteins that are predominantly cytoplasmic or predominantly nuclear, presumably depending on the subcellular localization of the ALK fusion partner. Notably, a TPM3-ALK oncogene was reported recently in anaplastic lymphoma, and TPM3-ALK is thereby the first known fusion oncogene that transforms, in vivo, both mesenchymal and lymphoid human cell lineages.