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A high-risk BAP1-mutant group and a favorable PBRM1-mutant group have been identified as mutation-defined subgroups of clear-cell renal cell carcinoma with differing clinical outcomes.
Why is the PBRM1-mutant group more advantageous and the BAP1-mutant group more risky?
Different clinical behaviors are displayed by clear-cell renal-cell carcinomas. However, it is unknown what molecular genetic processes underlie these behaviors. We found that PBRM1 and BAP1 mutations are largely mutually exclusive and that BAP1 is mutated in roughly 15% of clear-cell renal-cell carcinomas.
145 patients from the University of Texas Southwestern Medical Center in the United States who had primary clear-cell renal cell carcinoma and known PBRM1 and BAP1 mutation status were evaluated between 1998 and 2011 for this retrospective investigation. We used The Cancer Genome Atlas (TCGA second )'s independent cohort (n = 327) for validation.
Those with BAP1-mutant tumors had considerably lower median overall survival in the UTSW cohort than patients with PBRM1-mutant tumors. Despite being rare (three in the UTSW cohort and four in the TCGA cohort), patients with mutations in both PBRM1 and BAP1 had the lowest overall survival.
These findings lay the groundwork for a molecular genetic classification of clear-cell renal cell carcinoma that may have an impact on future treatment choices.
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