PT - JOURNAL ARTICLE AU - Daniela Nachmanson AU - Adam Officer AU - Hidetoshi Mori AU - Jonathan Gordon AU - Mark F. Evans AU - Joseph Steward AU - Huazhen Yao AU - Thomas O’Keefe AU - Farnaz Hasteh AU - Gary S. Stein AU - Kristen Jepsen AU - Donald L. Weaver AU - Gillian L. Hirst AU - Brian L. Sprague AU - Laura J. Esserman AU - Alexander D. Borowsky AU - Janet L. Stein AU - Olivier Harismendy TI - The breast pre-cancer atlas illustrates the molecular and micro-environmental diversity of ductal carcinoma in situ AID - 10.1101/2021.05.11.443641 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.05.11.443641 4099 - http://biorxiv.org/content/early/2021/06/07/2021.05.11.443641.short 4100 - http://biorxiv.org/content/early/2021/06/07/2021.05.11.443641.full AB - Micro-environmental and molecular factors mediating the progression of Breast Ductal Carcinoma In Situ (DCIS) are not well understood, impeding the development of prevention strategies and the safe testing of treatment de-escalation. We addressed methodological barriers and characterized the mutational, transcriptional, histological and microenvironmental landscape across 85 multiple micro-dissected regions from 39 cases. Most somatic alterations, including whole genome duplications, were clonal, but genetic divergence increased with physical distance. Phenotypic and subtype heterogeneity frequently associated with underlying genetic heterogeneity and regions with low-risk features preceded those with high-risk features according to the inferred phylogeny. B- and T-lymphocytes spatial analysis identified 3 immune states, including an epithelial excluded state located preferentially at DCIS regions, and characterized by histological and molecular features of immune escape, independently from molecular subtypes. Such breast pre-cancer atlas with uniquely integrated observations will help scope future expansion studies and build finer models of outcomes and progression risk.Competing Interest StatementThe authors have declared no competing interest.