GRM1 is upregulated through gene fusion and promoter swapping in chondromyxoid fibroma.
Author
Summary, in English
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.
Department/s
- Genetic chaos in aggressive cancer
- Division of Clinical Genetics
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2014
Language
English
Pages
474-477
Publication/Series
Nature Genetics
Volume
46
Issue
5
Links
Document type
Journal article
Publisher
Nature Publishing Group
Topic
- Medical Genetics
Status
Published
Research group
- Genetic chaos in aggressive cancer
ISBN/ISSN/Other
- ISSN: 1546-1718