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

Microenvironmental 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 mutation...

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Published inNPJ breast cancer Vol. 8; no. 1; pp. 6 - 13
Main Authors Nachmanson, Daniela, Officer, Adam, Mori, Hidetoshi, Gordon, Jonathan, Evans, Mark F., Steward, Joseph, Yao, Huazhen, O’Keefe, Thomas, Hasteh, Farnaz, Stein, Gary S., Jepsen, Kristen, Weaver, Donald L., Hirst, Gillian L., Sprague, Brian L., Esserman, Laura J., Borowsky, Alexander D., Stein, Janet L., Harismendy, Olivier
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 13.01.2022
Nature Publishing Group
Nature Portfolio
Subjects
692/4028/67/1347
692/53/2422
Biomedical and Life Sciences
Biomedicine
Breast cancer
Cancer Research
Cancer therapies
Cell Biology
Gene expression
Genomes
Histology
Human Genetics
Immunology
Laboratories
Medical screening
Medicine
Mutation
Oncology
Pathology
Surgery
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Summary:Microenvironmental 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 microdissected regions from 39 cases. Most somatic alterations, including whole-genome duplications, were clonal, but genetic divergence increased with physical distance. Phenotypic and subtype heterogeneity was 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 three 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.
ISSN:2374-4677
2374-4677
DOI:10.1038/s41523-021-00365-y