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Nat Genet. 2014 May;46(5):474-7. doi: 10.1038/ng.2927. Epub 2014 Mar 23.

GRM1 is upregulated through gene fusion and promoter swapping in chondromyxoid fibroma.

Author information

  • 1Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden.
  • 2Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden.
  • 3Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
  • 4Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.

Abstract

Glutamate receptors are well-known actors in the central and peripheral nervous systems, and altered glutamate signaling is implicated in several neurological and psychiatric disorders. It is increasingly recognized that such receptors may also have a role in tumor growth. Here we provide direct evidence of aberrant glutamate signaling in the development of a locally aggressive bone tumor, chondromyxoid fibroma (CMF). We subjected a series of CMFs to whole-genome mate-pair sequencing and RNA sequencing and found that the glutamate receptor gene GRM1 recombines with several partner genes through promoter swapping and gene fusion events. The GRM1 coding region remains intact, and 18 of 20 CMFs (90%) showed a more than 100-fold and up to 1,400-fold increase in GRM1 expression levels compared to control tissues. Our findings unequivocally demonstrate that direct targeting of GRM1 is a necessary and highly specific driver event for CMF development.

PMID:
24658000
[PubMed - indexed for MEDLINE]
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