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

AI Article Synopsis

  • The study investigates the factors influencing the progression of Breast Ductal Carcinoma In Situ (DCIS) by analyzing various molecular and microenvironmental characteristics from 39 cases.
  • It reveals that most genetic alterations are clonal, but genetic diversity increases with distance between tumor regions, indicating a complex evolutionary history of the cancer.
  • The research identifies three immune states within the DCIS microenvironment, including one associated with immune evasion, which could inform future strategies for prevention and treatment of breast cancer.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8758681PMC
http://dx.doi.org/10.1038/s41523-021-00365-yDOI Listing

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