Pd16-09 Germline Bap1 Mutations and Renal Cell Carcinoma: Clinical Course and Outcomes From 11 Patients

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (PD16)1 May 2024PD16-09 GERMLINE BAP1 MUTATIONS AND RENAL CELL CARCINOMA: CLINICAL COURSE AND OUTCOMES FROM 11 PATIENTS Lina Posada Calderon, Mark T. Dawidek, Lennert Einsman, Marc Ganz, Jonathan A. Coleman, Alvin Goh, Paul Russo, Ed Reznik, Yingbei Chen, Victor Reuter, A. Ari Hakimi, and Maria I. Carlo Lina Posada CalderonLina Posada Calderon , Mark T. DawidekMark T. Dawidek , Lennert EinsmanLennert Einsman , Marc GanzMarc Ganz , Jonathan A. ColemanJonathan A. Coleman , Alvin GohAlvin Goh , Paul RussoPaul Russo , Ed ReznikEd Reznik , Yingbei ChenYingbei Chen , Victor ReuterVictor Reuter , A. Ari HakimiA. Ari Hakimi , and Maria I. CarloMaria I. Carlo View All Author Informationhttps://doi.org/10.1097/01.JU.0001009560.23593.56.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: BRCA1-associated protein-1 (BAP1), is a gene frequently mutated in sporadic renal cell carcinoma (RCC) and associated with poor outcomes. Germline mutations in BAP1 cause BAP1-tumor predisposition syndrome (TPDS) and increased risk of RCC. Since BAP1 TPDS was recently described, the phenotype and clinical course of associated RCCs is largely unknown, with correspondingly limited published data and recommendations. We aim to describe clinical and genomic characteristics in RCC patients with BAP1 germline mutations seen at Memorial Sloan Kettering Cancer Center (MSKCC). METHODS: We retrospectively queried genetics and genitourinary databases from Jan 1990 to June 2022 who underwent germline testing at MSKCC or were seen in the genetics clinic, to identify those with germline BAP1 mutations and renal masses. We collected clinical and family history, histopathologic data, and oncological outcomes. Co-mutations were also analyzed for those with available genomic data. RCC specific survival was analyzed using the Kaplan–Meier method. RESULTS: Among 41 patients with BAP1 TPDS, 11 patients (26.8%) had a total of 20 renal masses. Median age at time of first RCC diagnosis was 53 years (interquartile range [IQR] 41-62), and the earliest presentation at 36 years old. Although 12 (60%) of the tumors were clear cell, one patient presented with synchronous clear cell and chromophobe RCC, and BAP1 deletion was confirmed in both tumors. Papillary RCC was exclusively seen in one patient with multifocal disease, who also developed a clear cell RCC. The smallest lesion that resulted in metastatic spread was 3 cm. Four patients (36%) developed more than 1 kidney tumor in their life, and two developed metachronous metastatic disease with a median tumor size of 7.0 cm (IQR 3.5–9.3). Three patients died of metastatic RCC, and the median kidney cancer specific survival was 207 months. The most frequent co-mutations in clear cell RCC were VHL (71.4%), PIK3CG (28.6%), KMT2C (14.3%), SETD2 (14.3%) among others, and no other mutations were observed in the chromophobe RCC. CONCLUSIONS: Patients with BAP1 TPDS present with RCC at a younger age than the median population RCC patients, and about one third of patients will have more than one kidney mass in their lifetime. This supports early screening and lifelong surveillance for second primary tumors. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e368 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Lina Posada Calderon More articles by this author Mark T. Dawidek More articles by this author Lennert Einsman More articles by this author Marc Ganz More articles by this author Jonathan A. Coleman More articles by this author Alvin Goh More articles by this author Paul Russo More articles by this author Ed Reznik More articles by this author Yingbei Chen More articles by this author Victor Reuter More articles by this author A. Ari Hakimi More articles by this author Maria I. Carlo More articles by this author Expand All Advertisement PDF downloadLoading ...