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

Genes Chromosomes Cancer. 2003 May;37(1):58-71. doi: 10.1002/gcc.10207.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Base Sequence / genetics
  • COS Cells
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Catalytic Domain / genetics
  • Chlorocebus aethiops
  • Chromosome Deletion*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 6 / genetics*
  • Glioblastoma / enzymology*
  • Glioblastoma / genetics*
  • Golgi Matrix Proteins
  • Humans
  • Membrane Glycoproteins / genetics
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Membrane Transport Proteins
  • Molecular Sequence Data
  • Molecular Weight
  • Oncogene Proteins, Fusion / chemistry
  • Oncogene Proteins, Fusion / genetics*
  • Protein Biosynthesis
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics*
  • Reading Frames / genetics
  • Receptor Protein-Tyrosine Kinases / chemistry
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Tumor Cells, Cultured

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • GOPC protein, human
  • Golgi Matrix Proteins
  • Golgi membrane glycoproteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • ROS1 protein, human
  • Receptor Protein-Tyrosine Kinases