A recurrent chromosome translocation breakpoint in breast and pancreatic cancer cell lines targets the neuregulin/NRGI gene
A recurrent chromosome translocation breakpoint in breast and pancreatic cancer cell lines targets the neuregulin/NRGI gene
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DOI：
10.1002/gcc.10218
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发表时间：
2003-08-01
影响因子：
3.7
通讯作者：
Chaffanet, M
中科院分区：
文献类型：
--
作者：
Adélaïde, J;Huang, HE;Chaffanet, M
8p11-21区域是乳腺癌和其他癌症发生改变的常见靶点。我们用多色荧光原位杂交（M-FISH）和bac特异性FISH检测了34个乳腺肿瘤细胞系和9个胰腺癌细胞系的这一区域的变化。我们描述了一个针对8p12上NRG1基因的复发性染色体易位断点。NRG1编码神经调节蛋白/heregulin-1家族的生长因子，这些生长因子是ERBB家族酪氨酸激酶受体的配体。在四种乳腺肿瘤细胞系中发现了NRG1基因的断点：ZR-75-1，在dic中（8;11）；HCC1937，在t(8; 10)(p12;p12.1)；SUM-52, in an hsr(8)(p12)；UACC-812, in a t(3;8)；在两种胰腺癌细胞系中：PaTu I，在a (8)t（4;8）中；和SUIT-2，在a del(8)(p)中。双色FISH图谱显示，这些断裂分布在NRG1基因的1.1 Mb范围内。我们已经知道，MDA-MB-175乳腺肿瘤细胞系具有dic(8; 11)，在NRG1中有一个断点，将NRG1与11q13上的DOC4基因融合。因此，我们在两种类型的癌细胞系中发现了总共7个断点，这些断点以NRG1基因为靶点。这表明NRG1位点是癌症易位的反复发生的靶点。逆转录细胞系rna的PCR分析揭示了NRG1转录物的广泛复杂性，但未能在具有NRG1断点的细胞系中检测到一致的mRNA亚型模式。(C) 2003 Wiley-Liss, Inc。
The 8p11-21 region is a frequent target of alterations in breast cancer and other carcinomas. We surveyed 34 breast tumor cell lines and 9 pancreatic cancer cell lines for alterations of this region by use of multicolor fluorescence in situ hybridization (M-FISH) and BAC-specific FISH. We describe a recurrent chromosome translocation breakpoint that targets the NRG1 gene on 8p12. NRG1 encodes growth factors of the neuregulin/heregulin-1 family that are ligands for tyrosine kinase receptors of the ERBB family. Breakpoints within the NRG1 gene were found in four of the breast tumor cell lines: ZR-75-1, in a dic(8; 11); HCC1937, in a t(8; 10)(p12;p12.1); SUM-52, in an hsr(8)(p12); UACC-812, in a t(3;8); and in two of the pancreatic cancer cell lines: PaTu I, in a der(8)t(4;8); and SUIT-2, in a del(8)(p). Mapping by two-color FISH showed that the breaks were scattered over 1.1 Mb within the NRG1 gene. It is already known that the MDA-MB-175 breast tumor cell line has a dic(8; 11), with a breakpoint in NRG1 that fuses NRG1 to the DOC4 gene on 11q13. Thus, we have found a total of seven breakpoints, in two types of cancer cell lines, that target the NRG1 gene. This suggests that the NRG1 locus is a recurring target of translocations in carcinomas. PCR analysis of reverse-transcribed cell line RNAs revealed an extensive complexity of the NRG1 transcripts but failed to detect a consistent pattern of mRNA isoforms in the cell lines with NRG1 breakpoint. (C) 2003 Wiley-Liss, Inc.