Integrative analyses reveal signaling pathways underlying familial breast cancer susceptibility

摘要: The signaling events that drive familial breast cancer (FBC) risk remain poorly understood. While the majority of genomic studies have focused on genetic variants, known variants account for at most 30% FBC cases. Considering multiple genes may influence risk, we hypothesized a pathway‐based strategy examining different data types from tissues could elucidate biological basis FBC. In this study, performed integrated analyses gene expression and exome‐sequencing peripheral blood mononuclear cells showed cell adhesion pathways are significantly consistently dysregulated in women who develop dysregulation high‐risk was also identified by profiling applied to normal tissue two independent cohorts. results our were validated primary mammary epithelial control women, using cell‐based functional assays, drug‐response fluorescence microscopy, Western blotting assays. Both experiments indicate cell–cell cell–extracellular matrix processes seem be disrupted non‐malignant high suggest potential role these development. ![][1] A integrative analysis transcriptomic datasets follow‐up experimental validations cancer. Mol Syst Biol. (2016) 12: 860 [1]: /embed/graphic-1.gif