Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility

In this study, we performed integrated analyses of gene expression and exome-sequencing data from peripheral blood mononuclear cells and showed that cell adhesion pathways are significantly and consistently dysregulated in women who develop FBC. The dysregulation of cell adhesion pathways in high-risk women was also identified by pathway-based profiling applied to normal breast tissue data from two independent cohorts. The results of our genomic analyses were validated in normal primary mammary epithelial cells from high-risk and control women, using cell-based functional assays, drug-response assays, fluorescence microscopy, and Western blotting assays. Both genomic and cell-based experiments indicate that cell–cell and cell–extracellular matrix adhesion processes seem to be disrupted in non-malignant cells of women at high risk for FBC and suggest a potential role for these processes in FBC development.

Source: Molecular Systems Biology - March 9, 2016 Category: Molecular Biology Authors: Piccolo, S. R., Hoffman, L. M., Conner, T., Shrestha, G., Cohen, A. L., Marks, J. R., Neumayer, L. A., Agarwal, C. A., Beckerle, M. C., Andrulis, I. L., Spira, A. E., Moos, P. J., Buys, S. S., Johnson, W. E., Bild, A. H. Tags: Cancer, Genome-Scale & Integrative Biology Articles Source Type: research