Publications by authors named "J S Brugge"
Organoid cultures offer a powerful technology to investigate many different aspects of development, physiology, and pathology of diverse tissues. Unlike standard tissue culture of primary breast epithelial cells, breast organoids preserve the epithelial lineages and architecture of the normal tissue. However, existing organoid culture methods are tedious, difficult to scale, and do not robustly retain estrogen receptor (ER) expression and responsiveness in long-term culture.
View Article and Find Full Text PDFThe prevalence and nature of somatic copy number alterations (CNAs) in breast epithelium and their role in tumor initiation and evolution remain poorly understood. Using single-cell DNA sequencing (49,238 cells) of epithelium from BRCA1 and BRCA2 carriers or wild-type individuals, we identified recurrent CNAs (for example, 1q-gain and 7q, 10q, 16q and 22q-loss) that are present in a rare population of cells across almost all samples (n = 28). In BRCA1/BRCA2 carriers, these occur before loss of heterozygosity (LOH) of wild-type alleles.
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- Germline BRCA1 mutation carriers have a high breast cancer risk, but the reasons for this increased risk are not fully understood.
- Researchers used a genetically engineered mouse model to show that the early onset of tumors in BRCA1 heterozygous mice can't be explained by the traditional "two-hit" hypothesis alone.
- Advanced techniques like single-cell RNA sequencing revealed distinct chromatin alterations in normal Brca1 heterozygous cells, hinting at epigenetic changes that might promote cancer, with specific transcription factors identified as key players in tumor development.
Organoid cultures offer a powerful technology to investigate many different aspects of development, physiology, and pathology of diverse tissues. Unlike standard tissue culture of primary breast epithelial cells, breast organoids preserve the epithelial lineages and architecture of the normal tissue. However, existing organoid culture methods are tedious, difficult to scale, and do not robustly retain estrogen receptor (ER) expression and responsiveness in long-term culture.
View Article and Find Full Text PDF