MP39-09 GENOMIC CHARACTERIZATION OF AGGRESSIVE SPORADIC EPITHELIOID ANGIOMYOLIPOMA

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I (MP39)1 Sep 2021MP39-09 GENOMIC CHARACTERIZATION OF AGGRESSIVE SPORADIC EPITHELIOID ANGIOMYOLIPOMA Phillip M Rappold, Mark Zucker, Angela Yoo, Benjamin Davelman, Kate Weiss, Paul Russo, Jonathan Coleman, Martin H Voss, Timothy A Chan, Robert J Motzer, Yingbei Chen, Ed Reznik, Satish K Tickoo, and A Ari Hakimi Phillip M RappoldPhillip M Rappold More articles by this author , Mark ZuckerMark Zucker More articles by this author , Angela YooAngela Yoo More articles by this author , Benjamin DavelmanBenjamin Davelman More articles by this author , Kate WeissKate Weiss More articles by this author , Paul RussoPaul Russo More articles by this author , Jonathan ColemanJonathan Coleman More articles by this author , Martin H VossMartin H Voss More articles by this author , Timothy A ChanTimothy A Chan More articles by this author , Robert J MotzerRobert J Motzer More articles by this author , Yingbei ChenYingbei Chen More articles by this author , Ed ReznikEd Reznik More articles by this author , Satish K TickooSatish K Tickoo More articles by this author , and A Ari HakimiA Ari Hakimi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002054.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Angiomyolipomas (AMLs) are the most common benign renal neoplasm with a strong female predilection, and occur as sporadic, isolated entities in the majority of cases. Among AML subtypes, epithelioid AMLs (eAMLs) can exhibit a malignant phenotype with potential for invasive growth and distant metastasis. There is conflicting data regarding whether conventional pathologic morphometric features accurately predict invasive and/or metastatic behavior. We sought to utilize next-generation sequencing of a series of primary and metastatic tumors to gain insight into the genomic features associated with aggressive eAML. METHODS: A query of our institutional sequencing cohort (MSK-IMPACT) was performed identify patients with AML/eAML. We calculated the fraction genome altered (FGA) and compared between metastatic and primary patients using the Wilcoxon/Mann-Whitney test. Copy number status was called using FACETS, and FGA was computed with respect to the IMPACT panel. RESULTS: Our query identified 10 patients with AML (median age 55; 6/10 female), and 3 patients with metastatic eAML (median age 47; 2/3 female). The median primary tumor size for AMLs was 2.15cm and 8.2cm for eAMLs. Mutations in TSC2 were the most common genomic alteration in our cohort seen in 12/13 primary tumors and 3/3 metastatic tumors. Two eAML tumors and two AML tumors exhibited LOH at the TSC2 locus. Truncating mutations in TP53 were seen in 2/3 eAML primary tumors and were clonal in the respective metastatic lesions from these patients. Alterations in ATRX, including a frameshift deletion and MAGT1-ATRX fusion, were seen in 2/3 eAML patients. An RB1 frameshift mutation was observed in 1/3 eAML patients. No TP53, ATRX, or RB1 alterations were present in AML tumors. Additional mutations seen in primary AML tumors included SMARCA4 (1/13) and PTCH1 (1/13). Median FGA did not differ between primary and metastatic tumors (p = 0.4484). CONCLUSIONS: Analysis of our cohort identified TSC2 as a common driver mutation in sporadic AML and eAML. Mutations in TP53, ATRX, and RB1 appear enriched in malignant eAML cases. Sequencing tumors from larger cohorts of eAML patients will be needed to validate these genomic features as possible biomarkers of malignant eAML. Source of Funding: NIH/NCI Cancer Center Support Grant (CCSG, P30 CA008748); Weiss Family Fund © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e708-e708 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Phillip M Rappold More articles by this author Mark Zucker More articles by this author Angela Yoo More articles by this author Benjamin Davelman More articles by this author Kate Weiss More articles by this author Paul Russo More articles by this author Jonathan Coleman More articles by this author Martin H Voss More articles by this author Timothy A Chan More articles by this author Robert J Motzer More articles by this author Yingbei Chen More articles by this author Ed Reznik More articles by this author Satish K Tickoo More articles by this author A Ari Hakimi More articles by this author Expand All Advertisement Loading ...