Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21)

被引:185
作者
Charest, A [1 ]
Lane, K [1 ]
McMahon, K [1 ]
Park, J [1 ]
Preisinger, E [1 ]
Conroy, H [1 ]
Housman, D [1 ]
机构
[1] MIT, Ctr Canc Res, Cambridge, MA 02139 USA
关键词
D O I
10.1002/gcc.10207
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The transmembrane proto-oncogene receptor tyrosine kinase (RTK) ROS is an orphan receptor that is aberrantly expressed in neoplasms of the central nervous system. Here, we report the fusion of its carboxy-terminal kinase domain to the amino-terminal portion of a protein called FIG (Fused in Glioblastoma) in a human glioblastoma multiforme (GBM). By characterizing both FIG and ROS genes in normal and in U118MG GBM cells, we determined that an intra-chromosomal homozygous deletion of 240 kilobases on 6q21 is responsible for the formation of the FIG-ROS locus. The FIG-ROS transcript is encoded by 7 FIG exons and 9 ROS-derived exons. We also demonstrate that the FIG-ROS locus encodes for an in-frame fusion protein with a constitutively active kinase activity, suggesting that FIG-ROS may act as an oncogene. This is the first example of a fusion RTK protein that results from an intra-chromosomal deletion, and it represents the first fusion RTK protein isolated from a human astrocytoma. (C) 2003 Wiley-Liss, Inc.
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收藏
页码:58 / 71
页数:14
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