PD51-03 MOLECULAR CHARACTERISTICS OF METASTATIC TERATOMAS AND MATCHED PRIMARY TESTICULAR GERM CELL TUMORS

Abstract

You have accessJournal of UrologyCME1 May 2022PD51-03 MOLECULAR CHARACTERISTICS OF METASTATIC TERATOMAS AND MATCHED PRIMARY TESTICULAR GERM CELL TUMORS Anna Savelyeva, Feng Wang, Lei Guo, John Lafin, Liwei Jia, Kirill Medvedev, Cheryl Lewis, Payal Kapur, Vitaly Margulis, Solomon Woldu, Xiaosong Meng, Nick Grishin, James Amatruda, Lin Xu, and Aditya Bagrodia Anna SavelyevaAnna Savelyeva More articles by this author , Feng WangFeng Wang More articles by this author , Lei GuoLei Guo More articles by this author , John LafinJohn Lafin More articles by this author , Liwei JiaLiwei Jia More articles by this author , Kirill MedvedevKirill Medvedev More articles by this author , Cheryl LewisCheryl Lewis More articles by this author , Payal KapurPayal Kapur More articles by this author , Vitaly MargulisVitaly Margulis More articles by this author , Solomon WolduSolomon Woldu More articles by this author , Xiaosong MengXiaosong Meng More articles by this author , Nick GrishinNick Grishin More articles by this author , James AmatrudaJames Amatruda More articles by this author , Lin XuLin Xu More articles by this author , and Aditya BagrodiaAditya Bagrodia More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002622.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Metastatic teratoma (MT) is a subtype of germ cell tumor (GCT) characterized by resistance to platinum-based chemotherapy. MT is treated via complete surgical excision, using retroperitoneal lymph node dissection (RPLND), following chemotherapy. Molecular characterization of post-chemotherapy MTs along with pre-chemotherapy testicular primary tumors could reveal 1) the mechanisms of MT development and differentiation, 2) molecular changes associated with platinum-resistance, 3) novel therapeutic options for patients with unresectable MTs. METHODS: We performed whole exome and transcriptome sequencing for 16 primary germ cell tumors and 18 metastatic teratomas, 11 were matched tumor/metastasis pairs. All MTs in our cohort were collected after induction platinum-based chemotherapy. We used VarScan for SNV analysis and PennCNV to detect genomic copy-number variations (CNVs). Metastatic Teratomas were compared to matched primary tumors and primary teratomas characterized by TCGA. RESULTS: Our analysis revealed that metastatic teratomas as well as their tumors of origin had low tumor mutation burden (0.65 and 0.47 accordingly). Amongst 583 SNVs detected in the study cohort, only two (KRAS p.Gly12Asp and KRAS p.Gly12Val) were previously described as oncogenic. Analysis of SNVs in proteins playing key roles in oncogenic signaling showed that TP53 and Ras pathways were the most affected in metastatic teratomas. The majority of metastatic teratomas possess gain of 3p11.1 and loss of 10q26.3, 16p11.2, 19p13.2, 19q12 and 22q12.3 loci. Within 3p11.1 we did not identify any well-known oncodrivers. However, 5 chromosomal loci with lost heterozygosity contained 16 previously annotated tumor suppressor genes: HTRA1, EBF3, FUS, PRKCB, NUPR1, PYCARD, ZNF668, ARMC5, YPEL3, DNMT1, DNAJB1, SMARCA4, GADD45GIP1, MIR199A1, TIMP3, TMPRSS6. Amongst those, GADD45GIP1 inhibition (growth arrest and DNA-damage-inducible, gamma interacting protein 1) is associated with cisplatin resistance development through mechanism of cellular senescence. CONCLUSIONS: Metastatic teratoma in our cohort is characterized by low tumor mutational burden and several recurring copy number changes. Molecular insight of metastatic teratoma may inform disease biology and treatment. Source of Funding: Dedman Scholar Award © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e843 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anna Savelyeva More articles by this author Feng Wang More articles by this author Lei Guo More articles by this author John Lafin More articles by this author Liwei Jia More articles by this author Kirill Medvedev More articles by this author Cheryl Lewis More articles by this author Payal Kapur More articles by this author Vitaly Margulis More articles by this author Solomon Woldu More articles by this author Xiaosong Meng More articles by this author Nick Grishin More articles by this author James Amatruda More articles by this author Lin Xu More articles by this author Aditya Bagrodia More articles by this author Expand All Advertisement PDF DownloadLoading ...