软骨样纤维瘤中 GRM1 基因重排的检测:荧光原位杂交、RNA 测序和免疫组化分析的比较。

IF 3.9 2区 医学 Q2 CELL BIOLOGY
Histopathology Pub Date : 2024-12-01 Epub Date: 2024-06-18 DOI:10.1111/his.15248
Dianne Torrence, Josephine K Dermawan, Yanming Zhang, Chad Vanderbilt, Sinchun Hwang, Kerry Mullaney, Achim Jungbluth, Mamta Rao, Kate Gao, Purvil Sukhadia, Konstantinos Linos, Narasimhan Agaram, Meera Hameed
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引用次数: 0

摘要

目的:软骨瘤样纤维瘤(CMF)是一种罕见的良性骨肿瘤,主要发生于青壮年,有时在诊断上具有挑战性。谷氨酸代谢受体 1(GRM1)基因编码一种代谢型谷氨酸受体,最近通过基因融合和启动子交换被证明在软骨瘤纤维瘤中上调。本研究旨在检测 CMF 病例中是否存在 GRM1 基因重排、基因融合和 GRM1 蛋白过表达:对部分病例使用 GRM1 断裂探针进行荧光原位杂交(FISH)检测,采用靶向 RNA 测序方法,并使用 GRM1 蛋白抗体进行免疫组化研究。两例病例进行了全转录组测序。在 13 例病例中,有 13 例通过使用 GRM1 抗体进行免疫组化检测到 GRM1 蛋白过度表达。在通过 FISH 成功检测的 12 个病例中,有 9 个病例通过断裂探针检测发现了 GRM1 重排。在检测的 8 个病例中,靶向 RNA 测序分析均未检测到基因融合,但所有 8 个病例的 GRM1 mRNA 表达均有所增加。对两个病例进行了全转录组测序(WTS),结果显示 GRM1 表达升高,但没有发现基因融合:结论:约75%的病例可通过FISH断裂探针检测到GRM1基因重排,免疫组化检测GRM1蛋白过度表达是一种敏感的诊断方法。基因融合未能通过靶向 RNA 测序检测出来,很可能是由于融合机制的复杂性,目前还不是临床确诊 CMF 的可靠方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Detection of GRM1 gene rearrangements in chondromyxoid fibroma: a comparison of fluorescence in-situ hybridisation, RNA sequencing and immunohistochemical analysis.

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.

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来源期刊
Histopathology
Histopathology 医学-病理学
CiteScore
10.20
自引率
4.70%
发文量
239
审稿时长
1 months
期刊介绍: Histopathology is an international journal intended to be of practical value to surgical and diagnostic histopathologists, and to investigators of human disease who employ histopathological methods. Our primary purpose is to publish advances in pathology, in particular those applicable to clinical practice and contributing to the better understanding of human disease.
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