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

Hansén Nord, KarolinLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine (author)

AuthorCount:10;
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.

Lilljebjörn, HenrikLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)tmb-hli (author)
Vezzi, FrancescoStockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab)(Swepub:su)fvezz (author)
Nilsson, JennyLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-jno (author)
Magnusson, LindaLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)mphy-lma (author)
Tayebwa, JohnboscoLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)med-jta (author)
de Jong, Danielle (author)
Bovee, Judith V. M. G. (author)
Hogendoorn, Pancras C. W. (author)
Szuhai, Karoly (author)
Avdelningen för klinisk genetikInstitutionen för laboratoriemedicin (creator_code:org_t)

In:Nature Genetics: Springer Science and Business Media LLC46:5, s. 474-4771061-40361546-1718

By the author/editor: Hansén Nord, Kar ...; Lilljebjörn, Hen ...; Vezzi, Francesco; Nilsson, Jenny; Magnusson, Linda; Tayebwa, Johnbos ...; show more...; de Jong, Daniell ...; Bovee, Judith V. ...; Hogendoorn, Panc ...; Szuhai, Karoly; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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