外周T细胞淋巴瘤伴t(4;12)(p16;p13)染色体易位中ETV6与成纤维细胞生长因子受体3的融合

Fusion of ETV6 to fibroblast growth factor receptor 3 in peripheral T-cell lymphoma with a t(4;12)(p16;p13) chromosomal translocation.

作者信息

Yagasaki F, Wakao D, Yokoyama Y, Uchida Y, Murohashi I, Kayano H, Taniwaki M, Matsuda A, Bessho M

机构信息

First Department of Internal Medicine, Saitama Medical School, Saitama, Japan.

出版信息

Cancer Res. 2001 Dec 1;61(23):8371-4.

PMID:11731410

Abstract

Fusions of the ETV6/TEL gene to receptor or protein tyrosine kinases (TKs), such as PDGFRbeta, JAK2, ABL, ABL2, TRKC, and Syk, have been reported in various hematological malignancies. Expression of the resultant chimeric proteins is believed to lead to constitutive TK activity through activation by the helix-loop-helix (HLH) domain of ETV6. We identified a novel ETV6 partner gene, fibroblast growth factor receptor 3 (FGFR3), in a patient with peripheral T-cell lymphoma (PTCL) with a t(4;12)(p16;p13) translocation. The ETV6-FGFR3 transcript showed a fusion of exon 5 of ETV6 to exon 10 of FGFR3, resulting in an open reading frame for a chimeric protein consisting of the HLH domain of ETV6 and the TK domains of FGFR3. This is the first report of ETV6 and FGFR3 involvement in PTCL.

摘要

在各种血液系统恶性肿瘤中，已报道ETV6/TEL基因与受体或蛋白酪氨酸激酶（TKs）发生融合，如血小板衍生生长因子受体β（PDGFRβ）、Janus激酶2（JAK2）、Abelson鼠白血病病毒癌基因1（ABL）、ABL2、神经营养酪氨酸激酶受体3（TRKC）和脾酪氨酸激酶（Syk）。据信，所产生的嵌合蛋白的表达通过ETV6的螺旋-环-螺旋（HLH）结构域激活而导致组成性TK活性。我们在一名患有t(4;12)(p16;p13)易位的外周T细胞淋巴瘤（PTCL）患者中鉴定出一个新的ETV6伙伴基因，即成纤维细胞生长因子受体3（FGFR3）。ETV6-FGFR3转录本显示ETV6的第5外显子与FGFR3的第10外显子融合，产生了一个由ETV6的HLH结构域和FGFR3的TK结构域组成的嵌合蛋白的开放阅读框。这是关于ETV6和FGFR3参与PTCL的首次报道。