Related Experiment Video
Updated: Jul 17, 2026
Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Characterization of a 3;6 translocation associated with renal cell carcinoma
Rebecca E Foster1, Mahera Abdulrahman, Mark R Morris
1Department of Medical and Molecular Genetics, University of Birmingham, The Medical School, Birmingham B15 2TT, UK.
Abstract:
The most frequent cause of familial clear cell renal cell carcinoma (RCC) is von Hippel-Lindau disease and the VHL tumor suppressor gene (TSG) is inactivated in most sporadic clear cell RCC. Although there is relatively little information on the mechanisms of tumorigenesis of clear cell RCC without VHL inactivation, a subset of familial cases harbors a balanced constitutional chromosome 3 translocation. To date nine different chromosome 3 translocations have been associated with familial or multicentric clear cell RCC; and in three cases chromosome 6 was also involved. To identify candidate genes for renal tumorigenesis we characterized a constitutional translocation, t(3;6)(q22;q16.1) associated with multicentric RCC without evidence of VHL target gene dysregulation. Analysis of breakpoint sequences revealed a 1.3-kb deletion on chromosome 6 within the intron of a 2 exon predicted gene (NT_007299.434). However, RT-PCR analysis failed to detect the expression of this gene in lymphoblast, fibroblast, or kidney tumor cell lines. No known genes were disrupted by the translocation breakpoints but several candidate TSGs (e.g., EPHB1, EPHA7, PPP2R3A RNF184, and STAG1) map within close proximity to the breakpoints.
Insights
Familial clear cell renal cell carcinoma (RCC) can arise from chromosome 3 translocations, independent of VHL gene inactivation. Researchers identified a novel translocation disrupting a chromosome 6 gene, suggesting new pathways in kidney cancer development.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Clear cell renal cell carcinoma (RCC) is frequently linked to von Hippel-Lindau (VHL) disease and VHL tumor suppressor gene (TSG) inactivation.
- Familial cases of RCC sometimes involve chromosome 3 translocations, suggesting alternative tumorigenesis pathways.
- Understanding these alternative mechanisms is crucial for identifying new therapeutic targets.
Observation:
- A constitutional translocation, t(3;6)(q22;q16.1), was analyzed in multicentric RCC cases without VHL dysregulation.
- Breakpoint analysis revealed a deletion on chromosome 6 within an intron of a predicted gene (NT_007299.434).
- This predicted gene was not expressed in tested cell lines, and no known genes were directly disrupted by the translocation.
Findings:
- The translocation t(3;6)(q22;q16.1) is associated with multicentric RCC.
- A novel deletion on chromosome 6 was identified near candidate tumor suppressor genes.
- Several potential tumor suppressor genes (TSGs) are located near the translocation breakpoints.
Implications:
- This study identifies a novel genetic alteration in familial RCC, expanding our understanding beyond VHL inactivation.
- Candidate TSGs near the breakpoints warrant further investigation as potential drivers of renal tumorigenesis.
- These findings may lead to new diagnostic markers or therapeutic strategies for specific RCC subtypes.
