Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation
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Summary
This summary is machine-generated.Clear-cell renal-cell carcinoma (ccRCC) subtypes with BAP1 mutations indicate a poorer prognosis, while those with PBRM1 mutations suggest a more favorable outcome. These findings support a molecular classification for ccRCC to guide future treatment strategies.
Area Of Science
- Oncology
- Genetics
- Molecular Biology
Background
- Clear-cell renal-cell carcinoma (ccRCC) exhibits variable clinical behaviors, with underlying molecular drivers largely unknown.
- BAP1 mutations occur in approximately 15% of ccRCC cases and are generally mutually exclusive with PBRM1 mutations.
- Understanding the clinicopathological significance of BAP1 and PBRM1 mutations is crucial for ccRCC subtyping.
Purpose Of The Study
- To investigate the clinicopathological significance of BAP1 and PBRM1 mutation status in ccRCC.
- To determine if BAP1-mutant and PBRM1-mutant ccRCC tumors are associated with different overall survival rates.
Main Methods
- Retrospective analysis of 145 primary ccRCC patients from UTSW, with PBRM1 and BAP1 mutation status defined.
- Classification of patients into BAP1-mutant and PBRM1-mutant groups.
- Validation using an independent cohort of 327 patients from The Cancer Genome Atlas (TCGA).
Main Results
- In the UTSW cohort, median overall survival was significantly shorter for BAP1-mutant tumors (4.6 years) compared to PBRM1-mutant tumors (10.6 years).
- Similar survival differences were observed in the TCGA cohort, with BAP1-mutant tumors showing shorter survival (1.9 years) than PBRM1-mutant tumors (5.4 years).
- Patients with mutations in both BAP1 and PBRM1 exhibited the worst overall survival in both cohorts.
Conclusions
- Mutation-defined subtypes of ccRCC, specifically BAP1-mutant (high-risk) and PBRM1-mutant (favorable), have distinct clinical outcomes.
- These findings provide a basis for a molecular genetic classification of ccRCC that could impact future treatment decisions.
- Consideration of these distinct molecular subtypes is essential for the design and evaluation of clinical studies in ccRCC.