Poster #95 - Cameron Cloud

The Stability of Epigenetic Cell Identity in Cancer

Cameron Cloud, BS Center for Computational and Genomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA Benjamin Steinberg, BS Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, Israel Tzachi Reizel, PhD Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, Israel Wanding Zhou, PhD Center for Computational and Genomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA

Cell-type-specific DNA methylation patterns encode cell identity and are largely preserved over mitotic divisions across the organism's lifespan. These patterns have shown strong potential as diagnostic markers in cancer. However, DNA methylation is also plastic, dynamically remodeled in development and diseases, including cancer, due to interaction with genetic, cellular, and environmental factors. Despite wide utilities, a unified and quantitative framework for assessing the stability of cell-identity-defining methylation signatures during tumorigenesis is lacking. Here, we systematically quantified the extent to which the DNA methylation-based definitions of cell identity, as established in healthy tissue, are maintained or disrupted in 300+ human cancer types. We found that cell-type-specific methylation signatures are remarkably stable across diverse cancer types, including metastatic lesions and tumors harboring mutations in epigenetic regulators. While signature erosions were common, particularly in in-vitro cell lines, complete loss in primary tumors was rare and often pointed to mischaracterized or ambiguous cells of origin. Our findings deepen the understanding of epigenetic maintenance in cancer and guide the development of more robust methylation-based cancer diagnosis.