GRM1 is upregulated through gene fusion and promoter swapping in chondromyxoid fibroma
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Date
2014
Journal Title
Journal ISSN
Volume Title
Publisher
Nature genetics
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.
Description
Keywords
GRM1, Gene fusion, Chondromyxoid fibroma
Citation
Nord, K. H., Lilljebjörn, H., Vezzi, F., Nilsson, J., Magnusson, L., Tayebwa, J., ... & Szuhai, K. (2014). GRM1 is upregulated through gene fusion and promoter swapping in chondromyxoid fibroma. Nature genetics, 46(5), 474-477. doi:10.1038/ng.2927