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Updated: May 3, 2026

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Loss of BRM expression is a frequently observed event in poorly differentiated clear cell renal cell carcinoma
Qiu-Yuan Xia1, Qiu Rao, Liang Cheng
1Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Aims:
The aim of this study was to examine the status of Brahma (BRM), a key SWI/SNF complex subunit, in clear cell renal cell carcinomas (RCCs), and to analyse the histopathology, immunophenotype, molecular features and prognosis of the BRM-negative cases.
Methods And Results:
We identified 19 cases of grade 4 tumours lacking BRM expression among 625 clear cell RCCs. All 19 cases exhibited features of poor differentiation: 13 showed pure poorly differentiated morphology, while six were composite tumours with an admixed typical low-grade component. Besides negative BRM expression, the immunophenotype of these cases was similar to clear cell RCC. VHL gene mutations were identified in nine of the 19 patients (47%). Chromosome 3p deletion was detected in 11 of 13 poorly differentiated RCCs and both areas of five of five composite tumours. All poorly differentiated tumour areas showed polysomy of chromosome 3. No losses or gains of chromosome 3 were observed in low-grade tumour areas of five of five composite RCCs.
Conclusions:
We have shown that loss of BRM expression is a common feature among poorly differentiated tumours in clear cell RCCs. We hypothesize that loss of BRM expression is involved in tumor de-differentiation in clear cell RCCs and may play an important role during tumour progression.
Insights
Loss of Brahma (BRM) expression is common in poorly differentiated clear cell renal cell carcinomas (RCCs). This finding suggests BRM loss may drive tumor de-differentiation and progression in clear cell RCC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The SWI/SNF chromatin remodeling complex plays a crucial role in gene regulation.
- Brahma (BRM) is a key catalytic subunit of the SWI/SNF complex.
- Alterations in SWI/SNF subunits are implicated in various cancers.
Purpose of the Study:
- To investigate the expression status of Brahma (BRM) in clear cell renal cell carcinomas (RCCs).
- To analyze the histopathology, immunophenotype, molecular characteristics, and prognosis of BRM-negative clear cell RCC cases.
- To understand the potential role of BRM loss in tumor de-differentiation and progression.
Main Methods:
- Retrospective analysis of 625 clear cell RCC cases.
- Identification of tumors lacking BRM expression.
- Histopathological and immunophenotypic assessment.
- Analysis of VHL gene mutations and chromosome 3p deletions.
- Detection of chromosome polysomy.
Main Results:
- 19 cases (3%) of grade 4 clear cell RCCs lacked BRM expression.
- These BRM-negative tumors exhibited poor differentiation, with 13 showing pure poorly differentiated morphology and six being composite tumors.
- VHL mutations (47%) and chromosome 3p deletions (in 11/13 poorly differentiated and all composite tumors) were observed.
- Poorly differentiated areas showed chromosome 3 polysomy, while low-grade areas in composite tumors did not show chromosome 3 alterations.
Conclusions:
- Loss of BRM expression is a frequent characteristic of poorly differentiated clear cell RCCs.
- BRM loss is hypothesized to be involved in the de-differentiation process of clear cell RCC.
- BRM expression status may be an important factor in clear cell RCC tumor progression.
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