Abstract B016: Aberrant age-related methylation leads to tumor predisposition in colorectal organoids

Abstract

Abstract Aging is one of the greatest risk factors for cancers, and epigenetic changes involving DNA methylation show close similarities during age-related cellular processes and tumor development. We have shown orthogonal relationships between the accrual of aberrant DNA methylation changes associated with cell division cycles during senescence and transformation. Consequently, we have hypothesized that while both senescent and proliferative aging cells coexist in the same tissues, the risk for cancer most likely comes from, and due to, epigenetic changes occurring in the latter, long-term, self-renewing cells. Using colon organoid models, we have studied the importance of genes undergoing DNA methylation mediated silencing during aging and their role in predisposing to tumorigenesis. Analyses of the in vivo and ex vivo aging-associated epigenetic/expression changes indicate the importance of age-related aberrant methylation in tumor promoting states. Citation Format: Daniel A. Petkovich, Rachael Powers, Yong Tao, Byunghak Kang Nibedita Patel, Kathy Gabrielson, Rafael de Cabo, Stephen B. Baylin, Hariharan P. Easwaran. Aberrant age-related methylation leads to tumor predisposition in colorectal organoids [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr B016.