BARD1 and Breast Cancer: the Possibility of Creating Screening Tests and New Preventive and Therapeutic Pathways for Predisposed Women

Abstract

Current oncological developments are based on improved understanding of genetics, and especially the discovery of genes whose alterations affect cell functions with consequences for the whole body. Our work is focused on the most important of these genes, the BARD1 and its oncogenic role in breast cancer. Most importantly, the study points to new avenues in the treatment and prevention of the most frequent female cancer based on BARD1 research. The BARD1 and BRCA1 proteins have similar structures and functions, and they combine to form the new molecule BARD1-BRCA1 heterodimer. Through ubiquitination, this heterodimer has significant effects on individual proteins, enabling, among others, the destruction of damaged DNA fragments. Ubiquitination, as well as stabilizing chromatin, or regulating the number of centrosomes, confirms the protective cooperation of BARD1 and BRCA1 in the stabilization of the genome. The overexpression of the oncogenic isoforms BARD1β and BARD1δ permit cancer development. The introduction of routine tests, for instance, to identify the presence of the BARD1β isoform, would make it possible to detect patients at high risk of developing cancer. On the other hand, introducing BARD1δ isoform blocking therapy, which would reduce estrogen sensitivity, may be a new line of cancer therapy with potential to modulate responses to existing treatments. It is possible that the BARD 1 gene offers new hope for improving breast cancer therapy.

The Fundamental Role of BARD1 Mutations and Their Applications as a Prognostic Biomarker for Cancer Treatment

“…The Fundamental Role of BARD1 Mutations and Their Applications as a Prognostic Biomarker… DOI: http://dx.doi.org/10.5772/intechopen.107143 these actions help FL-BARD1 to play a tumor suppressor role, in contrast to reports that BARD1 isoforms such as BARD1 work against this function and accelerate cancer development [41].…”

“…According to the European study, the BARD1 mutation, one of the most prevalent non-BRCA1/2 mutations, was identified in 10901 TNBC cases and demonstrated a significant contribution to TNBC propensity with an incidence of 0.5−0.7%. Furthermore, Caucasian PVs American carriers of BARD1 gene pathological variants were at lower risk of TNBC (21%) than African American carriers of BARD1 gene mutations (39%) [41,68].…”

“…BARD1 has about 19 distinct expressed isoforms that have been identified so far [12,44]; several of these isoforms, including BARD1β, BARD1κ, and BARD1π, have been implicated in the development of cancer by an oncogenic role [12,13]. At the same time, it has been noted that the FL-BARD1, either on its own or in combination with BRCA1, has a tumor suppressor function [41]. However, BARD1β and BARD1δ were previously reported to have an antagonistic effect on full-length BARD1, resulting in oncogenicity and cancer susceptibility [12].…”

Identification of a novel pathogenic variant in PALB2 and BARD1 genes by a multigene sequencing panel in triple negative breast cancer in Morocco

“…An interesting approach might be radiogenomics, which brings together the clinical assessment, imaging results, and the genetic background [74]. This approach would be of interest in relation to the immunohistochemical staining of the BARD1 gene, which in turn can be imaged inmagnetic resonance scans [75].…”