Rxivist logo

The breast pre-cancer atlas illustrates the molecular and micro-environmental diversity of ductal carcinoma in situ

By Daniela Nachmanson, Adam Officer, Hidetoshi Mori, Jonathan Gordon, Mark F. Evans, Joseph Steward, Huazhen Yao, Thomas O'Keefe, Farnaz Hasteh, Gary S Stein, Kristen Jepsen, Donald L. Weaver, Gillian Hirst, Brian L. Sprague, Laura J. Esserman, Alexander D Borowsky, Janet L Stein, Olivier Harismendy

Posted 12 May 2021
bioRxiv DOI: 10.1101/2021.05.11.443641

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.

Download data

  • Downloaded 405 times
  • Download rankings, all-time:
    • Site-wide: 83,893
    • In genomics: 5,448
  • Year to date:
    • Site-wide: 17,498
  • Since beginning of last month:
    • Site-wide: 25,862

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide