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Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors
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-...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Nature Publishing Group UK
2018
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232171/ https://www.ncbi.nlm.nih.gov/pubmed/30420702 http://dx.doi.org/10.1038/s41467-018-06925-4 |
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| author | Ratnaparkhe, Manasi Wong, John K. L. Wei, Pei-Chi Hlevnjak, Mario Kolb, Thorsten Simovic, Milena Haag, Daniel Paul, Yashna Devens, Frauke Northcott, Paul Jones, David T. W. 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, Aurélie |
| author_facet | Ratnaparkhe, Manasi Wong, John K. L. Wei, Pei-Chi Hlevnjak, Mario Kolb, Thorsten Simovic, Milena Haag, Daniel Paul, Yashna Devens, Frauke Northcott, Paul Jones, David T. W. 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, Aurélie |
| author_sort | Ratnaparkhe, Manasi |
| collection | PubMed |
| 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 tumors with complex genomic rearrangements. |
| format | Online Article Text |
| id | pubmed-6232171 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2018 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-62321712018-11-14 Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors Ratnaparkhe, Manasi Wong, John K. L. Wei, Pei-Chi Hlevnjak, Mario Kolb, Thorsten Simovic, Milena Haag, Daniel Paul, Yashna Devens, Frauke Northcott, Paul Jones, David T. W. 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, Aurélie Nat Commun Article 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. Nature Publishing Group UK 2018-11-12 /pmc/articles/PMC6232171/ /pubmed/30420702 http://dx.doi.org/10.1038/s41467-018-06925-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Ratnaparkhe, Manasi Wong, John K. L. Wei, Pei-Chi Hlevnjak, Mario Kolb, Thorsten Simovic, Milena Haag, Daniel Paul, Yashna Devens, Frauke Northcott, Paul Jones, David T. W. 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, Aurélie Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors |
| title | Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors |
| title_full | Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors |
| title_fullStr | Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors |
| title_full_unstemmed | Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors |
| title_short | Defective DNA damage repair leads to frequent catastrophic genomic events in murine and human tumors |
| title_sort | defective dna damage repair leads to frequent catastrophic genomic events in murine and human tumors |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232171/ https://www.ncbi.nlm.nih.gov/pubmed/30420702 http://dx.doi.org/10.1038/s41467-018-06925-4 |
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