TY - JOUR
T1 - More than bad luck
T2 - Cancer and aging are linked to replication-driven changes to the epigenome
AU - Minteer, Christopher J.
AU - Thrush, Kyra
AU - Gonzalez, John
AU - Niimi, Peter
AU - Rozenblit, Mariya
AU - Rozowsky, Joel
AU - Liu, Jason
AU - Frank, Mor
AU - McCabe, Thomas
AU - Higgins-Chen, Albert T.
AU - Hofstatter, Erin
AU - Pusztai, Lajos
AU - Beckman, Kenneth
AU - Gerstein, Mark
AU - Levine, Morgan E.
N1 - Publisher Copyright:
Copyright © 2023 The Authors, some rights reserved.
PY - 2023/7/21
Y1 - 2023/7/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85165321655&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85165321655&partnerID=8YFLogxK
U2 - 10.1126/SCIADV.ADF4163
DO - 10.1126/SCIADV.ADF4163
M3 - Article
C2 - 37467337
AN - SCOPUS:85165321655
SN - 2375-2548
VL - 9
JO - Science Advances
JF - Science Advances
IS - 29
M1 - eadf4163
ER -
