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More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome
Aging is a leading risk factor for cancer. While it is proposed that age-related accumulation of somatic mutations drives this relationship, it is likely not the full story. We show that aging and cancer share a common epigenetic replication signature, which we modeled using DNA methylation from ext...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10355820/ https://www.ncbi.nlm.nih.gov/pubmed/37467337 http://dx.doi.org/10.1126/sciadv.adf4163 |
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author | Minteer, Christopher J. Thrush, Kyra Gonzalez, John Niimi, Peter Rozenblit, Mariya Rozowsky, Joel Liu, Jason Frank, Mor McCabe, Thomas Higgins-Chen, Albert T. Hofstatter, Erin Pusztai, Lajos Beckman, Kenneth Gerstein, Mark Levine, Morgan E. |
author_facet | Minteer, Christopher J. Thrush, Kyra Gonzalez, John Niimi, Peter Rozenblit, Mariya Rozowsky, Joel Liu, Jason Frank, Mor McCabe, Thomas Higgins-Chen, Albert T. Hofstatter, Erin Pusztai, Lajos Beckman, Kenneth Gerstein, Mark Levine, Morgan E. |
author_sort | Minteer, Christopher J. |
collection | PubMed |
description | Aging is a leading risk factor for cancer. While it is proposed that age-related accumulation of somatic mutations drives this relationship, it is likely not the full story. We show that aging and cancer share a common epigenetic replication signature, which we modeled using DNA methylation from extensively passaged immortalized human cells in vitro and tested on clinical tissues. This signature, termed CellDRIFT, increased with age across multiple tissues, distinguished tumor from normal tissue, was escalated in normal breast tissue from cancer patients, and was transiently reset upon reprogramming. In addition, within-person tissue differences were correlated with predicted lifetime tissue-specific stem cell divisions and tissue-specific cancer risk. Our findings suggest that age-related replication may drive epigenetic changes in cells and could push them toward a more tumorigenic state. |
format | Online Article Text |
id | pubmed-10355820 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-103558202023-07-20 More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome Minteer, Christopher J. Thrush, Kyra Gonzalez, John Niimi, Peter Rozenblit, Mariya Rozowsky, Joel Liu, Jason Frank, Mor McCabe, Thomas Higgins-Chen, Albert T. Hofstatter, Erin Pusztai, Lajos Beckman, Kenneth Gerstein, Mark Levine, Morgan E. Sci Adv Biomedicine and Life Sciences Aging is a leading risk factor for cancer. While it is proposed that age-related accumulation of somatic mutations drives this relationship, it is likely not the full story. We show that aging and cancer share a common epigenetic replication signature, which we modeled using DNA methylation from extensively passaged immortalized human cells in vitro and tested on clinical tissues. This signature, termed CellDRIFT, increased with age across multiple tissues, distinguished tumor from normal tissue, was escalated in normal breast tissue from cancer patients, and was transiently reset upon reprogramming. In addition, within-person tissue differences were correlated with predicted lifetime tissue-specific stem cell divisions and tissue-specific cancer risk. Our findings suggest that age-related replication may drive epigenetic changes in cells and could push them toward a more tumorigenic state. American Association for the Advancement of Science 2023-07-19 /pmc/articles/PMC10355820/ /pubmed/37467337 http://dx.doi.org/10.1126/sciadv.adf4163 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). 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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Minteer, Christopher J. Thrush, Kyra Gonzalez, John Niimi, Peter Rozenblit, Mariya Rozowsky, Joel Liu, Jason Frank, Mor McCabe, Thomas Higgins-Chen, Albert T. Hofstatter, Erin Pusztai, Lajos Beckman, Kenneth Gerstein, Mark Levine, Morgan E. More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome |
title | More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome |
title_full | More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome |
title_fullStr | More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome |
title_full_unstemmed | More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome |
title_short | More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome |
title_sort | more than bad luck: cancer and aging are linked to replication-driven changes to the epigenome |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10355820/ https://www.ncbi.nlm.nih.gov/pubmed/37467337 http://dx.doi.org/10.1126/sciadv.adf4163 |
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