More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome
Menée à l'aide d'échantillons tissulaires et de lignées cellulaires d'astrocytes, cette étude met en évidence une corrélation entre une signature, basée sur l'évolution de la méthylation et de la réplication de l'ADN au cours du vieillissement, et le risque de cancer
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. Cellular replication leaves an epigenetic fingerprint that may partially underly the age-associated increase in cancer risk.
Science Advances , article en libre accès, 2022