目的:软骨粘液样纤维瘤(CMF)是一种罕见的,良性骨肿瘤,主要发生在年轻人中,偶尔在诊断上具有挑战性。谷氨酸代谢型受体1(GRM1)基因编码代谢型谷氨酸受体,最近显示通过基因融合和启动子交换在软骨粘液样纤维瘤中上调。这项研究的目的是询问CMF病例是否存在GRM1基因重排,基因融合和GRM1蛋白过表达。
结果:对选定的病例进行荧光原位杂交(FISH)与GRM1分离探针的测试,靶向RNA测序方法和GRM1蛋白抗体的免疫组织化学研究。对两个病例进行全转录组测序。在13个案例中,有13个使用GRM1抗体通过免疫组织化学检测GRM1蛋白过表达。在FISH测试成功的12例中,12个中的9个通过分解探针分析显示GRM1重排。靶向RNA测序分析在测试的8例病例中均未检测到基因融合,但在所有8例病例中GRM1mRNA表达均增加。进行全转录组测序(WTS)的两个病例显示GRM1表达升高,没有基因融合。
结论:在大约75%的病例中,使用FISH分离探针可以检测到GRM1基因重排,免疫组织化学检测GRM1蛋白过表达是一种灵敏的诊断方法。通过靶向RNA测序未检测到基因融合,很可能是由于融合机制的复杂性,并且还不是在临床上确认CMF诊断的可靠方法。
OBJECTIVE: 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.
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.
CONCLUSIONS: 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.