Evidence for accelerated aging in mammary epithelia of women carrying germline BRCA1 or BRCA2 mutations
Date
2021-09-14
Authors
Shalabi, Sundus F.
et al.
Journal Title
Journal ISSN
Volume Title
Publisher
Springer Nature Limited
Abstract
During aging in the human mammary gland, luminal epithelial cells lose lineage fidelity by expressing markers normally
expressed in myoepithelial cells. We hypothesize that loss of lineage fidelity is a general manifestation of epithelia that are
susceptible to cancer initiation. In the present study, we show that histologically normal breast tissue from younger women
who are susceptible to breast cancer, as a result of harboring a germline mutation in BRCA1, BRCA2 or PALB2 genes, exhibits
hallmarks of accelerated aging. These include proportionately increased luminal epithelial cells that acquired myoepithelial
markers, decreased proportions of myoepithelial cells and a basal differentiation bias or failure of differentiation of cKit+ pro-
genitors. High-risk luminal and myoepithelial cells are transcriptionally enriched for genes of the opposite lineage, inflam-
matory- and cancer-related pathways. We have identified breast-aging hallmarks that reflect a convergent biology of cancer
susceptibility, regardless of the specific underlying genetic or age-dependent risk or the associated breast cancer subtype.
Description
Keywords
Citation
Shalabi, S.F., Miyano, M., Sayaman, R.W. et al. Evidence for accelerated aging in mammary epithelia of women carrying germline BRCA1 or BRCA2 mutations. Nat Aging 1, 838–849 (2021). https://doi.org/10.1038/s43587-021-00104-9