Hahn Yoonsoo, Bera Tapan Kumar, Gehlhaus Kristen, Kirsch Ilan R, Pastan Ira H, Lee Byungkook
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA.
Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13257-61. doi: 10.1073/pnas.0405490101. Epub 2004 Aug 23.
Chromosomal rearrangements resulting in gene fusions are frequently involved in carcinogenesis. Here, we describe a semiautomatic procedure for identifying fusion gene transcripts by using publicly available mRNA and EST databases. With this procedure, we have identified 96 transcript sequences that are derived from 60 known fusion genes. Also, 47 or more additional sequences appear to be derived from 20 or more previously unknown putative fusion genes. We have experimentally verified the presence of a previously unknown IRA1/RGS17 fusion in the breast cancer cell line MCF7. The fusion gene encodes the full-length RGS17 protein, a regulator of G protein-coupled signaling, under the control of the IRA1 gene promoter. This study demonstrates that databases of ESTs can be used to discover fusion genes resulting from structural rearrangement of chromosomes.
导致基因融合的染色体重排频繁参与致癌过程。在此,我们描述了一种利用公开可用的mRNA和EST数据库鉴定融合基因转录本的半自动程序。通过该程序,我们鉴定出了96个转录本序列,它们来自60个已知的融合基因。此外,47个或更多的其他序列似乎来自20个或更多先前未知的假定融合基因。我们已经通过实验验证了乳腺癌细胞系MCF7中存在一种先前未知的IRA1/RGS17融合。该融合基因在IRA1基因启动子的控制下编码全长RGS17蛋白,RGS17蛋白是G蛋白偶联信号传导的调节剂。这项研究表明,EST数据库可用于发现由染色体结构重排产生的融合基因。