MP71-08 SELECT CONCURRENT CHROMOSOME 3P MUTATIONS PREDICT WORSE OVERALL AND RECURRENCE-FREE SURVIVAL IN CLEAR CELL RENAL CARCINOMA IN THE CANCER GENOME ATLAS

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I1 Apr 2016MP71-08 SELECT CONCURRENT CHROMOSOME 3P MUTATIONS PREDICT WORSE OVERALL AND RECURRENCE-FREE SURVIVAL IN CLEAR CELL RENAL CARCINOMA IN THE CANCER GENOME ATLAS Christopher Keith, John Petros, Michael Rossi, and Rebecca Arnold Christopher KeithChristopher Keith More articles by this author , John PetrosJohn Petros More articles by this author , Michael RossiMichael Rossi More articles by this author , and Rebecca ArnoldRebecca Arnold More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1454AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In clear cell renal cell carcinoma (ccRCC), mutations in BAP1 and, in some cohorts, PBRM1 are associated with worse survival, while VHL and SETD2 mutations do not independently predict poor prognosis. While studies have analyzed prognostic impact of independent mutations on these chromosome 3p (chr 3p) genes, the prognostic significance of co-existing mutations in these near-neighboring genes is unknown. METHODS The Cancer Genome Atlas (TCGA) ccRCC database was probed for mutations in VHL, BAP1, SETD2, and PBRM1. Kaplan-Meier survival log-rank and Cox multivariate analysis were performed. RESULTS Of the 418 patients with ccRCC in TCGA, at least one of the four chr 3p genes was mutated in 74% of cases. Co-existing somatic mutations in VHL and BAP1 (n=16), VHL and SETD2 (n=9), or PBRM1 and SETD2 and/or BAP1 (n=13) compared to all other cases was associated with worse recurrence-free (1.83 vs. 6.0 years; p=0.0004) and overall survival (2.42 vs. 7.13 years; p<0.0001). The survival difference remained significant after controlling for total mutational burden (p<0.0001), BAP1 mutations (p=0.014), and PBRM1 mutations (p<0.0001). On multivariate analysis, high-risk chromosome 3p status was associated with significantly decreased recurrence-free survival and overall survival. Interestingly, the deleterious effects of BAP1 in the ccRCC TCGA cohort are negated when the group with only coexisting VHL or PBRM1 mutations is excluded (p=0.83). When comparing the high-risk BAP1 group to all other cases with BAP1 alterations, there is a significant difference in survival (2.42 vs. 5.38 years; p=0.01). CONCLUSIONS Concurrent mutations in VHL and BAP1, VHL and SETD2, or PBRM with SETD2 and/or BAP1 are associated with significantly decreased recurrence-free and overall survival in ccRCC in the TCGA. In addition, the deleterious effect of BAP1 mutations in TCGA is dependent on concurrent chr 3p mutations. Such information may be useful in risk stratification of patients with ccRCC. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e918 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Christopher Keith More articles by this author John Petros More articles by this author Michael Rossi More articles by this author Rebecca Arnold More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...