Healthy BRCA1/2 mutation carriers exhibit a pre-CAF signature and altered epithelial marker expression in breast tissue.

ABSTRACT: Germline mutations in BRCA-1 and BRCA-2 significantly increase breast cancer risk. However, the mechanisms driving early tumorigenesis remain incompletely understood. While previous studies have primarily focused on luminal progenitors as tumor-initiating cells in BRCA-1 ^mut/+and BRCA-2 ^mut/+carriers, the impact of these mutations on the stromal microenvironment and their role in cancer initiation has notbeen thoroughly explored. We analyzed preneoplastic breast tissues from healthy BRCA-1 ^mut/+and BRCA-2 ^mut/+carriers, focusing on expression patterns and alterations of Podoplanin (PDPN), CD10, and programmed cell death ligand 2 (PD-L2) across both epithelial and stromal compartments. Our findings reveal a high prevalence of pre-CAF (PDPN^hig

SUBMITTER: De Leonardis F 

PROVIDER: S-EPMC12460555 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature