{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ratnaparkhe M"],"funding":["Fritz Thyssen Stiftung","NCI NIH HHS","NINDS NIH HHS","Fritz Thyssen Stiftung (Fritz Thyssen Foundation)"],"pagination":["4760"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6232171"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(1)"],"pubmed_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 tum"],"journal":["Nature communications"],"pubmed_title":["Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors."],"pmcid":["PMC6232171"],"funding_grant_id":["P30 CA021765","P01 CA096832","Az.10.17.2.030MN","R01 NS037956"],"pubmed_authors":["Haag D","Kolb T","Kool M","Simovic M","Mlynarski W","Zapatka M","Jones DTW","Downing SM","Pfister SM","Wei PC","Ratnaparkhe M","Korshunov A","Kumar R","McKinnon PJ","Paul Y","Lichter P","Northcott P","Wong JKL","Jauch A","Ernst A","Alt FW","Hlevnjak M","Pastorczak A","Devens F"],"additional_accession":[]},"is_claimable":false,"name":"Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors.","description":"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 tum","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Nov","modification":"2026-07-15T19:04:19.157Z","creation":"2026-07-09T03:10:24.496Z"},"accession":"S-EPMC6232171","cross_references":{"pubmed":["30420702"],"doi":["10.1038/s41467-018-06925-4"]}}