The breast pre-cancer atlas illustrates the molecular and micro-environmental diversity of ductal carcinoma in situ.
Journal
NPJ breast cancer
ISSN: 2374-4677
Titre abrégé: NPJ Breast Cancer
Pays: United States
ID NLM: 101674891
Informations de publication
Date de publication:
13 Jan 2022
13 Jan 2022
Historique:
received:
26
06
2021
accepted:
06
12
2021
entrez:
14
1
2022
pubmed:
15
1
2022
medline:
15
1
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35027560
doi: 10.1038/s41523-021-00365-y
pii: 10.1038/s41523-021-00365-y
pmc: PMC8758681
doi:
Types de publication
Journal Article
Langues
eng
Pagination
6Subventions
Organisme : NCI NIH HHS
ID : U01 CA196383
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008806
Pays : United States
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : T15LM011271
Organisme : NCI NIH HHS
ID : U01 CA196406
Pays : United States
Organisme : NLM NIH HHS
ID : T15 LM011271
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE026644
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA023100
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : U01CA196406
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : U01CA196383
Organisme : NIGMS NIH HHS
ID : U54 GM115516
Pays : United States
Organisme : Tobacco-Related Disease Research Program (TRDRP)
ID : 28DT-0011
Informations de copyright
© 2022. The Author(s).
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