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Ratnaparkhe, Manasi; Wong, John K.; Wei, Pei-Chi; Hlevnjak, Mario; Kolb, Thorsten; Simovic, Milena; Haag, Daniel; Paul, Yashna; Devens, Frauke; Northcott, Paul; Jones, David T.; Kool, Marcel; Jauch, Anna; Pastorczak, Agata; Mlynarski, Wojciech; Korshunov, Andrey; Kumar, Rajiv; Downing, Susanna M.; Pfister, Stefan M.; Zapatka, Marc; McKinnon, Peter J.; Alt, Frederick W.; Lichter, Peter; Ernst, Aurelie

Abstract 3496: Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors

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  • Medientyp: E-Artikel
  • Titel: Abstract 3496: Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors
  • Beteiligte: Ratnaparkhe, Manasi; Wong, John K.; Wei, Pei-Chi; Hlevnjak, Mario; Kolb, Thorsten; Simovic, Milena; Haag, Daniel; Paul, Yashna; Devens, Frauke; Northcott, Paul; Jones, David T.; Kool, Marcel; Jauch, Anna; Pastorczak, Agata; Mlynarski, Wojciech; Korshunov, Andrey; Kumar, Rajiv; Downing, Susanna M.; Pfister, Stefan M.; Zapatka, Marc; McKinnon, Peter J.; Alt, Frederick W.; Lichter, Peter; Ernst, Aurelie
  • Erschienen: American Association for Cancer Research (AACR), 2019
  • Erschienen in: Cancer Research, 79 (2019) 13_Supplement, Seite 3496-3496
  • Sprache: Englisch
  • DOI: 10.1158/1538-7445.am2019-3496
  • ISSN: 0008-5472; 1538-7445
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: Abstract Chromothripsis and chromoanasynthesis are catastrophic events leading to clustered genomic rearrangements. Whole-genome sequencing revealed frequent complex genomic rearrangements (n= 16/26) in brain tumors developing in mice deficient for factors involved in homologous recombination repair or non-homologous end-joining. Catastrophic events were tightly linked to Myc/Mycn amplification, with increased DNA damage and inefficient apoptotic response already observable at early postnatal stages. Inhibition of repair processes and comparison of the mouse tumors with human medulloblastomas (n=68) and glioblastomas (n=32) identified chromothripsis as associated with MYC/MYCN gains and with DNA repair deficiencies, pointing towards therapeutic opportunities to target DNA repair defects in tumors with complex genomic rearrangements. Citation Format: Manasi Ratnaparkhe, John K. Wong, Pei-Chi Wei, Mario Hlevnjak, Thorsten Kolb, Milena Simovic, Daniel Haag, Yashna Paul, Frauke Devens, Paul Northcott, David T. Jones, Marcel Kool, Anna Jauch, Agata Pastorczak, Wojciech Mlynarski, Andrey Korshunov, Rajiv Kumar, Susanna M. Downing, Stefan M. Pfister, Marc Zapatka, Peter J. McKinnon, Frederick W. Alt, Peter Lichter, Aurelie Ernst. Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3496.
  • Zugangsstatus: Freier Zugang