3. Network modeling and breast cancer risk

3. Network modeling and breast cancer riskBreast cancer is a heterogeneous disease that may initiate at different points in the epithelial differentiation hierarchy. Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. We have recently described a molecular network containing AURKA, BRCA1, and RHAMM that regulates mammary epithelial apicobasal polarization. Functional alteration of network components may be at the basis of an increased risk of estrogen receptor α-negative breast cancer. We aim to further decipher the role of RHAMM in mammary epithelial differentiation and to evaluate the role of other breast cancer susceptibility gene products in this setting. To this end, we combine omic data analyses with experimental evaluations to identify genetic interactions influencing breast cancer risk. In addition, we perform systems-level studies of interactome and transcriptome data directed at defining the fundamental properties of cancer development and progression.

To this study centered on HMMR/RHAMM, we are expanding the potential collection of susceptibility genes/alleles through integrated analyses of GWAS and omic data, and genetic studies within the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).