Our genome harbors epigenetic marks, such as DNA methylation (DNAm) at cytosine residues, which govern cellular differentiation. Some epigenetic modifications accumulate throughout life in a highly reproducible manner–they may contribute to the aging process and facilitate reliable age-predictions. So far, little is known how these “epigenetic aging signatures” are modified in cancer tissue and whether or not they are accelerated as compared to normal tissue. In this study, we systematically analyzed age-associated DNAm patterns in many types of cancer. In contrast to non-malignant tissue the epigenetic aging signatures hardly reflect chronological age of cancer patients. This may at least partially be attributed to the fact that cancer is a clonal disease capturing only the epigenetic make-up of the tumor-initiating cell. Notably, the aberrant DNAm patterns are not randomly distributed but reveal co-regulation at regions that become methylated upon aging in non-malignant tissue. Furthermore, we demonstrate that deviations of epigenetic age-predictions correlate with clinical parameters. In fact, they are clearly associated with overall survival in many types of cancer. These findings are particularly important, as they indicate relevance of age-associated DNA methylation patterns for malignant transformation, cancer development and prognosis.
Vyšlo v časopise: Epigenetic Aging Signatures Are Coherently Modified in Cancer. PLoS Genet 11(6): e32767. doi:10.1371/journal.pgen.1005334 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005334
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