Detection of GRM1 gene rearrangements in chondromyxoid fibroma: A comparison of fluorescence in-situ hybridisation, RNA sequencing and immunohistochemical analysis Journal Article
| Authors: | Torrence, D.; Dermawan, J. K.; Zhang, Y.; Vanderbilt, C.; Hwang, S.; Mullaney, K.; Jungbluth, A.; Rao, M.; Gao, K.; Sukhadia, P.; Linos, K.; Agaram, N.; Hameed, M. |
| Article Title: | Detection of GRM1 gene rearrangements in chondromyxoid fibroma: A comparison of fluorescence in-situ hybridisation, RNA sequencing and immunohistochemical analysis |
| Abstract: | Aims: Chondromyxoid fibroma (CMF) is a rare, benign bone tumour which arises primarily in young adults and is occasionally diagnostically challenging. Glutamate metabotropic receptor 1 (GRM1) gene encodes a metabotropic glutamate receptor and was recently shown to be up-regulated in chondromyxoid fibroma through gene fusion and promoter swapping. The aim of this study was to interrogate cases of CMF for the presence of GRM1 gene rearrangements, gene fusions and GRM1 protein overexpression. Methods and results: Selected cases were subjected to testing by fluorescent in-situ hybridisation (FISH) with a GRM1 break-apart probe, a targeted RNA sequencing method and immunohistochemical study with an antibody to GRM1 protein. Two cases were subjected to whole transcriptomic sequencing. In 13 of 13 cases, GRM1 protein overexpression was detected by immunohistochemistry using the GRM1 antibody. Of the 12 cases successfully tested by FISH, nine of 12 showed GRM1 rearrangements by break-apart probe assay. Targeted RNA sequencing analysis did not detect gene fusions in any of the eight cases tested, but there was an increase in GRM1 mRNA expression in all eight cases. Two cases subjected to whole transcriptomic sequencing (WTS) showed elevated GRM1 expression and no gene fusions. Conclusion: GRM1 gene rearrangements can be detected using FISH break-apart probes in approximately 75% of cases, and immunohistochemical detection of GRM1 protein over-expression is a sensitive diagnostic method. The gene fusion was not detected by targeted RNA sequencing, due most probably to the complexity of fusion mechanism, and is not yet a reliable method for confirming a diagnosis of CMF in the clinical setting. © 2024 John Wiley & Sons Ltd. |
| Keywords: | immunohistochemistry; adolescent; adult; child; clinical article; controlled study; human tissue; aged; bone neoplasms; middle aged; bone tumor; young adult; unclassified drug; genetics; clinical feature; histopathology; comparative study; metabolism; in situ hybridization, fluorescence; pathology; tumor marker; fluorescence in situ hybridization; gene rearrangement; diagnosis; gene fusion; fibroma; sequence analysis, rna; protein antibody; comparative effectiveness; procedures; humans; human; male; female; article; rna sequencing; biomarkers, tumor; metabotropic receptor; protein expression level; whole transcriptome sequencing; chondromyxoid fibroma; grm1 rearrangement and upregulation; receptors, metabotropic glutamate; glutamate metabotropic receptor 1; metabotropic receptor 1; metabotropic glutamate receptor type 1 |
| Journal Title: | Histopathology |
| Volume: | 85 |
| Issue: | 6 |
| ISSN: | 0309-0167 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2024-12-01 |
| Start Page: | 889 |
| End Page: | 898 |
| Language: | English |
| DOI: | 10.1111/his.15248 |
| PUBMED: | 38890779 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Meera Hameed -- Source: Scopus |
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