The inherent molecular stigma in normal breast tissue of BRCA1/2 gene mutation carriers: TC1 and SYNGR2 genes involvement in neoplastic transformatio

Mutations in a number of genes are now known to cause susceptibility to breast cancer. In the context of high-risk families, the most important genes are BRCA1 and BRCA2. Inherited mutations in BRCA1/2 may be necessary to explain the Mendelian pattern of breast cancer in some families but are not sufficient to completely describe interindividual variability in cancer risk. In this work we tried to identify possible modifier genes in a group of hereditary, sporadic breast cancers and controls by gene expression profiling. We show that normal breast tissues collected from hereditary breast cancer patients and from healthy BRCA1/2 gene mutation carriers reveal a significant different molecular profile compared to the normal tissue of sporadic breast cancer patients and healthy BRCA1/2 gene mutation non-carriers. The present study demonstrates that TC1 and SYNGR2 genes are statistically overexpressed not only in tumoral tissues but also in the normal tissues of hereditary breast cancer patients and in BRCA1/2 healthy carriers compared to sporadic breast cancer patients or healthy controls. Silencing of SYNGR2 and TC1 was performed on MCF7 breast cancer cell line to better understand their involvement in breast cancer. Our results suggest that normal mammary tissue of BRCA1/2 gene carriers could be another source for the discovery of other genetic determinants that favor hereditary cancer onset.