Mp04-05 nf2-mutant renal cell carcinoma: a clinical and genomic characterization of an unclassified carcinoma

You have accessJournal of UrologyCME1 Apr 2023MP04-05 NF2-MUTANT RENAL CELL CARCINOMA: A CLINICAL AND GENOMIC CHARACTERIZATION OF AN UNCLASSIFIED CARCINOMA Stephen W. Reese, Mark Zucker, Lennert Eismann, Katiana Vazquez-Rivera, Arnold Oparanozie, Robert Motzer, Martin H. Voss, Chung-Han Lee, Maria Carlo, Ritesh R. Kotecha, Victor Reuter, Jonathan Coleman, Paul Russo, Eduard Reznik, Ari A. Hakimi, and Yingbei Chen Stephen W. ReeseStephen W. Reese More articles by this author , Mark ZuckerMark Zucker More articles by this author , Lennert EismannLennert Eismann More articles by this author , Katiana Vazquez-RiveraKatiana Vazquez-Rivera More articles by this author , Arnold OparanozieArnold Oparanozie More articles by this author , Robert MotzerRobert Motzer More articles by this author , Martin H. VossMartin H. Voss More articles by this author , Chung-Han LeeChung-Han Lee More articles by this author , Maria CarloMaria Carlo More articles by this author , Ritesh R. KotechaRitesh R. Kotecha More articles by this author , Victor ReuterVictor Reuter More articles by this author , Jonathan ColemanJonathan Coleman More articles by this author , Paul RussoPaul Russo More articles by this author , Eduard ReznikEduard Reznik More articles by this author , Ari A. HakimiAri A. Hakimi More articles by this author , and Yingbei ChenYingbei Chen More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003215.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The use of genomic and molecular classification of renal cell carcinoma has led to an increasing appreciation of tumor biology and as well as characterization of previously unclassified subset of tumors. The importance of identifying specific drivers of tumorigenesis has wide-ranging implications for clinical care including risk stratification and treatment decision in the localized and systemic setting. We present a series of previously unclassified renal cell carcinoma patients that are primarily driven by a mutation in the NF2 gene. METHODS: We queried the MSK Clinical Sequencing Cohort, a database containing 95,499 samples who were sequenced using MSK-IMPACT, a DNA sequencing platform that captures 505 whole exome cancer genes. We found 37 patients with an NF2 mutation who had tumors designated as “unclassified” based on their pathology report. We also identified patients in our prospectively maintained surgical registry if they had undergone extirpative kidney surgery. RESULTS: Our cohort was notable for a median age at presentation of 64 years, male predominance (64.58%) and normal body habitus (BMI 25.5). At the time of presentation, mass size was noted to be small at 4.7 cm, however 25 (67.5%) of patients had metastatic disease a presentation. 14 patients underwent surgical resection of primary tumor, 9 of which were performed in the cytoreductive setting and most patients (n=10, 71.4%) had evidence of non-localized disease on surgical pathology. The median overall survival for the cohort was 29.6 months. We performed an additional stratification of patients with an NF2 mutation and concurrent 3p mutations (SETD2, PBRM1, BAP1). Median overall survival in the cohort was 28.2 mo. (95% CI: 15.5-NR). Survival amongst patients with an NF2 mutation alone was 29.6 mo. (95% CI: 19.6-NR) and patients with a concurrent 3p mutation had an overall survival of 16.5 mo. (95% CI: 6.2-NR). There was a non-specific trend for tumors with 3p mutations to have worse outcomes, however the log-rank differences between the two groups was not significant (p=0.06). Genomic analysis of sequenced tumors demonstrated that the NF2 mutant tumors have a low median MSI score (0.12) and low TMB score (3.9). CONCLUSIONS: We provide clinical and genomic characterization of a group of patients who were previously found to be unclassified renal cell carcinoma, however now found to have NF2 mutation as the putative driver of tumorigenesis. NF2 mutated renal cell carcinoma is an aggressive histology that undergoes early metastatic spread at small tumor size. Greater awareness of this tumor histology can lead to early identification and can help guide treatment decisions. Source of Funding: No funding © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e35 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Stephen W. Reese More articles by this author Mark Zucker More articles by this author Lennert Eismann More articles by this author Katiana Vazquez-Rivera More articles by this author Arnold Oparanozie More articles by this author Robert Motzer More articles by this author Martin H. Voss More articles by this author Chung-Han Lee More articles by this author Maria Carlo More articles by this author Ritesh R. Kotecha More articles by this author Victor Reuter More articles by this author Jonathan Coleman More articles by this author Paul Russo More articles by this author Eduard Reznik More articles by this author Ari A. Hakimi More articles by this author Yingbei Chen More articles by this author Expand All Advertisement PDF downloadLoading ...