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Copy number footprints of platinum-based anticancer therapies
Recently, distinct mutational footprints observed in metastatic tumors, secondary malignancies and normal human tissues have been demonstrated to be caused by the exposure to several chemotherapeutic drugs. These characteristic mutations originate from specific lesions caused by these chemicals to t...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9956877/ https://www.ncbi.nlm.nih.gov/pubmed/36780550 http://dx.doi.org/10.1371/journal.pgen.1010634 |
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author | Gonzalez, Santiago Lopez-Bigas, Nuria Gonzalez-Perez, Abel |
author_facet | Gonzalez, Santiago Lopez-Bigas, Nuria Gonzalez-Perez, Abel |
author_sort | Gonzalez, Santiago |
collection | PubMed |
description | Recently, distinct mutational footprints observed in metastatic tumors, secondary malignancies and normal human tissues have been demonstrated to be caused by the exposure to several chemotherapeutic drugs. These characteristic mutations originate from specific lesions caused by these chemicals to the DNA of exposed cells. However, it is unknown whether the exposure to these chemotherapies leads to a specific footprint of larger chromosomal aberrations. Here, we address this question exploiting whole genome sequencing data of metastatic tumors obtained from patients exposed to different chemotherapeutic drugs. As a result, we discovered a specific copy number footprint across tumors from patients previously exposed to platinum-based therapies. This footprint is characterized by a significant increase in the number of chromosomal fragments of copy number 1–4 and size smaller than 10 Mb in exposed tumors with respect to their unexposed counterparts (median 14–387% greater across tumor types). The number of chromosomal fragments characteristic of the platinum-associated CN footprint increases significantly with the activity of the well known platinum-related footprint of single nucleotide variants across exposed tumors. |
format | Online Article Text |
id | pubmed-9956877 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-99568772023-02-25 Copy number footprints of platinum-based anticancer therapies Gonzalez, Santiago Lopez-Bigas, Nuria Gonzalez-Perez, Abel PLoS Genet Research Article Recently, distinct mutational footprints observed in metastatic tumors, secondary malignancies and normal human tissues have been demonstrated to be caused by the exposure to several chemotherapeutic drugs. These characteristic mutations originate from specific lesions caused by these chemicals to the DNA of exposed cells. However, it is unknown whether the exposure to these chemotherapies leads to a specific footprint of larger chromosomal aberrations. Here, we address this question exploiting whole genome sequencing data of metastatic tumors obtained from patients exposed to different chemotherapeutic drugs. As a result, we discovered a specific copy number footprint across tumors from patients previously exposed to platinum-based therapies. This footprint is characterized by a significant increase in the number of chromosomal fragments of copy number 1–4 and size smaller than 10 Mb in exposed tumors with respect to their unexposed counterparts (median 14–387% greater across tumor types). The number of chromosomal fragments characteristic of the platinum-associated CN footprint increases significantly with the activity of the well known platinum-related footprint of single nucleotide variants across exposed tumors. Public Library of Science 2023-02-13 /pmc/articles/PMC9956877/ /pubmed/36780550 http://dx.doi.org/10.1371/journal.pgen.1010634 Text en © 2023 Gonzalez et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Gonzalez, Santiago Lopez-Bigas, Nuria Gonzalez-Perez, Abel Copy number footprints of platinum-based anticancer therapies |
title | Copy number footprints of platinum-based anticancer therapies |
title_full | Copy number footprints of platinum-based anticancer therapies |
title_fullStr | Copy number footprints of platinum-based anticancer therapies |
title_full_unstemmed | Copy number footprints of platinum-based anticancer therapies |
title_short | Copy number footprints of platinum-based anticancer therapies |
title_sort | copy number footprints of platinum-based anticancer therapies |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9956877/ https://www.ncbi.nlm.nih.gov/pubmed/36780550 http://dx.doi.org/10.1371/journal.pgen.1010634 |
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