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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
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.
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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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