MP11-17 ORIGIN OF GERM CELL TUMORS: SOMATIC TRANSFORMATION AND PRESENCE OF CANCER STEM-LIKE CELLS IN TERATOMA

Abstract

You have accessJournal of UrologyPenile & Testicular Cancer: Penile & Testicular Cancer I (MP11)1 Apr 2020MP11-17 ORIGIN OF GERM CELL TUMORS: SOMATIC TRANSFORMATION AND PRESENCE OF CANCER STEM-LIKE CELLS IN TERATOMA Eric Umbreit*, Christopher Wood, Andrew McIntosh, Mary Beth Westerman, Daniel Shapiro, Aron Joon, Miao Zhang, Jose Karam, and Shi-ming Tu Eric Umbreit*Eric Umbreit* More articles by this author , Christopher WoodChristopher Wood More articles by this author , Andrew McIntoshAndrew McIntosh More articles by this author , Mary Beth WestermanMary Beth Westerman More articles by this author , Daniel ShapiroDaniel Shapiro More articles by this author , Aron JoonAron Joon More articles by this author , Miao ZhangMiao Zhang More articles by this author , Jose KaramJose Karam More articles by this author , and Shi-ming TuShi-ming Tu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000831.017AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Controversy surrounds the genesis of germ cell-associated teratoma and the origin of its ability to transform into malignancy. It is unknown whether a teratoma dedifferentiates from a progeny cell into a progenitor cell or teratoma develops from cancer stem cells, enabling it to differentiate into multiple lineages. We hypothesize that somatic transformation occurs by differentiation of a progenitor stem-like cell embedded in the teratoma. METHODS: Two investigations where explored to further evaluate this hypothesis: (1) develop a post-chemotherapy teratoma primary culture and demonstrate a stem cell-like progenitor cell embedded within teratoma derived from surgically resected specimens, and (2) evaluate the genetic and molecular profiles of metastatic teratoma and corresponding malignant transformation. Flow cytometry was performed on live cells for cell-surface stem-ness markers to identify a potential cancer stem cell within teratoma. Second, archival tumor tissue from 7 patients with teratoma and its associated somatically transformed tumor was used for DNA and RNA sequencing. RESULTS: Teratoma cells were successfully grown in primary culture from two patients. Cells were confirmed as teratoma by final pathology and primary culture analysis for i12p, SALL4, OCT3 and NANOG. By flow cytometry, cell lines were found to have cells positive for the stem-ness markers CD24, CD26, CD34, CD44, CD90, CD117, Cripto-1, SSEA-1, and SSEA-4. In the second investigation arm using the T200 panel for DNA analysis, we identified 58 genes harboring mutations of which 24 genes indicated discordance between teratoma and somatic transformation. None of the 24 genes were consistently altered between patients, thus, teratoma and transformed tissue had similar genetic profiles. RNA analysis revealed 7 significant genes with increased expression in teratoma tissue compared to somatic transformation, suggesting a different epigenetic profile between tissue types. CONCLUSIONS: For the first time ever reported, we successfully created primary culture teratoma cell lines. In addition, we have begun to identify cancer stem-like cells within mature teratoma. By demonstrating that metastatic teratoma and their corresponding somatic transformations had similar if not identical genetic profiles, we hypothesize they have a common clonal origin. We propose an alternative hypothesis in which teratoma contains a stem-cell entity that could both differentiate into a teratoma or any other tumor phenotype. Source of Funding: None. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e142-e142 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eric Umbreit* More articles by this author Christopher Wood More articles by this author Andrew McIntosh More articles by this author Mary Beth Westerman More articles by this author Daniel Shapiro More articles by this author Aron Joon More articles by this author Miao Zhang More articles by this author Jose Karam More articles by this author Shi-ming Tu More articles by this author Expand All Advertisement PDF downloadLoading ...