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Rosemarie, Quincy

0000-0002-0394-1573

Mayo Clinic

Masonic Cancer Center, Department of Pediatrics, and Center for Genome Engineering, University of Minnesota, Minneapolis, Minnesota.

Citations 1

Sleeping Beauty Insertional Mutagenesis Reveals Important Genetic Drivers of Central Nervous System Embryonal Tumors
Beckmann, Pauline J. , Larsson, Alex T. , Ostergaard, Jason, Wagner, Sandra, Rahrmann, Eric P. , Shamsan, Ghaidan A. , Otto, George M. , Williams, Rory L. , Wang, Jun , Lee, Catherine , Tschida, Barbara R. , Das, Paramita , Dubuc, Adrian M. , Moriarity, Branden S. , Picard, Daniel , Wu, Xiaochong , Rosemarie, Quincy , Krebs, Ryan D., Molan, Amy M. , Demer, Addison M. , Frees, Michelle M. , Rizzardi, Anthony E., Schmechel, Stephen C. , Jenkins, Robert B. , Wechsler‐Reya, Robert J. , Odde, David J. , Taylor, Michael D. , Sarver, Aaron L. , Largaespada, David A. , Rahrmann, Eric P , Shamsan, Ghaidan A , Williams, Rory L , Picard, Daniel , Rosemarie, Quincy , Odde, David J , Larson, Jon D. , Wagner, Sandra, Tschida, Barbara R , Rodríguez, Fausto J. , Krebs, Ryan D., Eberhart, Charles G. , Huang, Annie , Largaespada, David A.

Cancer Research | January 23, 2019 | Volume: 79 | Issue: 5 | Pages: 905-917

10.1158/0008-5472.can-18-1261 Get It

Abstract Medulloblastoma and central nervous system primitive neuroectodermal tumors (CNS-PNET) are aggressive, poorly differentiated brain tumors with limited effective therapies. Using Sleeping Beauty (SB) transposon mutagenesis, we identified novel genetic drivers of medulloblastoma and CNS-PNET. Cross-species gene expression analyses classified SB-driven tumors into distinct medulloblastoma and CNS-PNET subgroups, indicating they resemble human Sonic hedgehog and group 3 and 4 medulloblastoma and CNS neuroblastoma with FOXR2 activation. This represents the first genetically induced mouse model of CNS-PNET and a rare model of group 3 and 4 medulloblastoma. We identified several putative proto-oncogenes including Arhgap36, Megf10, and Foxr2. Genetic manipulation of these genes demonstrated a robust impact on tumorigenesis in vitro and in vivo. We also determined that FOXR2 interacts with N-MYC, increases C-MYC protein stability, and activates FAK/SRC signaling. Altogether, our study identified several promising therapeutic targets in medulloblastoma and CNS-PNET. Significance: A transposon-induced mouse model identifies several novel genetic drivers and potential therapeutic targets in medulloblastoma and CNS-PNET.