1 BARD 1 and breast cancer : the possibility of creating 2 screening tests and new preventive and therapeutic 3 pathways for predisposed women 4

Current oncological developments are based on improved understanding of genetics, and 18 especially the discovery of genes whose alterations affect cell functions with consequences for the 19 whole body. Our work is focused on the one of these genes, the BARD1 and its oncogenic role in 20 breast cancer. Most importantly, the study points to new avenues in the treatment and prevention 21 of the most frequent female cancer based on BARD1 research. The BARD1 and BRCA1 proteins have 22 similar structures and functions, and they combine to form the new molecule BARD1-BRCA1 23 heterodimer. The BARD1-BRCA1 complex is involved in genetic stabilization at the cellular level. It 24 allows to mark abnormal DNA fragments by attaching ubiquitin to them. In addition, it blocks (by 25 ubiquitination of RNA polymerase II) the transcription of damaged DNA. Ubiquitination, as well 26 as stabilizing chromatin, or regulating the number of centrosomes, confirms the protective 27 cooperation of BARD1 and BRCA1 in the stabilization of the genome. The overexpression of the 28 oncogenic isoforms BARD1β and BARD1δ permit cancer development. The introduction of routine 29 tests, for instance, to identify the presence of the BARD1β isoform, would make it possible to detect 30 patients at high risk of developing cancer. On the other hand, introducing BARD1δ isoform blocking 31 therapy, which would reduce estrogen sensitivity, may be a new line of cancer therapy with 32 potential to modulate responses to existing treatments. It is possible that the BARD 1 gene offers 33 new hope for improving breast cancer therapy. 34