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Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21)
Author(s) -
Charest Alain,
Lane Keara,
McMahon Kevin,
Park Julie,
Preisinger Elizabeth,
Conroy Helen,
Housman David
Publication year - 2003
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.10207
Subject(s) - receptor tyrosine kinase , fusion protein , exon , protein kinase domain , biology , tyrosine kinase , transmembrane protein , microbiology and biotechnology , locus (genetics) , ror1 , fusion gene , gene , kinase , signal transduction , cancer research , receptor , genetics , platelet derived growth factor receptor , recombinant dna , growth factor , mutant
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 ( F used i n G lioblastoma) 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. © 2003 Wiley‐Liss, Inc.