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| Home > Publications database > Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors. |
| Home > Publications database > Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors. |
| Journal Article | DKFZ-2018-02012 |
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2018
Nature Publishing Group UK
[London]
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Please use a persistent id in citations: doi:10.1038/s41467-018-06925-4
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.
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