The t(1;9)(p34;q34) and t(8;12)(p11;q15) fuse pre-mRNA processing proteins SFPQ (PSF) and CPSF6 to ABL and FGFR1
The t(1;9)(p34;q34) and t(8;12)(p11;q15) fuse pre-mRNA processing proteins SFPQ (PSF) and CPSF6 to ABL and FGFR1
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DOI：
10.1002/gcc.20541
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发表时间：
2008-05-01
影响因子：
3.7
通讯作者：
Grand, Francis H.
中科院分区：
文献类型：
--
作者：
Hidalgo-Curtis, Claire;Chase, Andrew;Grand, Francis H.
我们研究了两例获得性染色体重排的患者，一名男性表现为t（1;9）（p34：q34）和B细胞祖细胞急性淋巴细胞白血病，一名女性表现为t（8;12）（p11;q15）和8 p11骨髓增殖综合征。我们确定了t（1;9）融合ABL到SFPQ（也称为PSF），SFPQ是一种定位于1 p34的基因，编码多聚嘧啶片段结合蛋白相关剪接因子。t（8; 12）融合CPSF 6（一种切割和多聚腺苷酸化特异性因子）至FGFR I。通过扩增基因组断裂点和RT-PCR证实融合。这些融合体的预测致癌产物SFPQ-ABL和CPSF 6-FGFR 1是符合读码框的，并编码配偶体蛋白的N-末端结构域和ABL和FGFR 1的整个酪氨酸激酶结构域和C-末端序列。SFPQ与两种FGFR I融合伴侣ZNF 198和CPSF 6相互作用，其在功能上与复发性PDGFR α伴侣FIP 1 L1相关。因此，我们的研究结果确定了一组蛋白质，这是重要的前mRNA加工作为融合伙伴的酪氨酸激酶在血液恶性肿瘤。(C)2008 Wiley-Liss，Inc.
We have investigated two patients with acquired chromosomal rearrangements, a male presenting with a t(1;9)(p34:q34) and B cell progenitor acute lymphoid leukemia and a female presenting with a t(8;12)(p11;q15) and the 8p11 myeloproliferative syndrome. We determined that the t(1;9) fused ABL to SFPQ (also known as PSF), a gene mapping to 1p34 that encodes a polypyrimidine tract-binding protein-associated splicing factor. The t(8; 12) fused CPSF6, a cleavage and polyadenylation specificity factor, to FGFR I. The fusions were confirmed by amplification of the genomic breakpoints and RT-PCR. The predicted oncogenic products of these fusions, SFPQ-ABL and CPSF6-FGFR1, are in-frame and encode the N-terminal domain of the partner protein and the entire tyrosine kinase domain and C-terminal sequences of ABL and FGFR1. SFPQ interacts with two FGFR I fusion partners, ZNF 198 and CPSF6, that are functionally related to the recurrent PDGFR alpha partner FIP1L1. Our findings thus identify a group of proteins that are important for pre-mRNA processing as fusion partners for tyrosine kinases in hematological malignancies. (C) 2008 Wiley-Liss, Inc.