Data from Global DNA Methylation Analysis of Cancer-Associated Fibroblasts Reveals Extensive Epigenetic Rewiring Linked with RUNX1 Upregulation in Breast Cancer Stroma

• DOI: 10.1158/0008-5472.c.6514163.v1
• Publication Date: 2023-03-31T18:29:42Z
• Authors: Coral Halperin; Joschka Hey; Dieter Weichenhan; Yaniv Stein; Shimrit Mayer; Pavlo Lutsik; Christoph Plass; Ruth Scherz-Shouval
• Keywords: RUNX1; Reprogramming; Cancer-Associated Fibroblasts

<div>Abstract<p>Cancer cells recruit and rewire normal fibroblasts in their microenvironment to become protumorigenic cancer-associated (CAF). These CAFs are genomically stable, yet transcriptional programs distinct from those of counterparts. Transcriptional regulation plays a major role this reprogramming, but the extent which epigenetic modifications DNA also contribute rewiring CAF transcription is not clear. Here we address question by dissecting landscape breast CAFs. Applying tagmentation-based whole-genome bisulfite sequencing mouse model cancer, found that undergo massive methylation changes as they transition into analyses revealed RUNX1 potential mediator process identified RUNX1-dependent stromal gene signature. Coculture models showed both its signature induced In cancer patients, was upregulated CAFs, expression associated with poor disease outcome, highlighting relevance these findings human disease. This work presents comprehensive genome-wide map reveals previously unknown facet dynamic plasticity stroma.</p>Significance:<p>The first cancer–associated unravels stroma, far-reaching therapeutic implications.</p></div>