Functional Variant rs4442975 Modulating FOXA1 Binding Affinity Can Influence Bone Marrow Suppression during Neoadjuvant Chemotherapy for Luminal A Type Breast Cancer.
ABC successfully identifies previously characterized functional SNVs, such as the rs4784227breast cancer risk associated SNP that modulates the affinity of FOXA1 for the chromatin.
A new study shows that SNPs associated with breast cancer risk are located in enhancer regions and alter binding affinity for the pioneer factor FOXA1.
Recently, the rs4442975 T-allele, which disrupts the recruitment of FOXA1 and interacts with the IGFBP5 promoter, was associated to BC susceptibility in a European population.
Biological assays indicated that the germline G>T variation at rs6506689 creates a FOXA1-binding site and up-regulates the expression of RAB31, thus playing an important role in the development of BC.
NBCs less frequently harboured PIK3CA mutations than common forms of ER<sup>+</sup> /HER2<sup>-</sup> , luminal A and invasive lobular carcinomas (p < 0.05), and showed a significantly higher frequency of somatic mutations affecting ARID1A (17% versus 2%, p < 0.05) and the transcription factor-encoding genes FOXA1 (17% versus 2%, p = 0.01) and TBX3 (17% versus 3%, p < 0.05) than common-type ER<sup>+</sup> /HER2<sup>-</sup> breast carcinomas.
Our results show that breast cancer risk-associated SNPs are enriched in the cistromes of FOXA1 and ESR1 and the epigenome of histone H3 lysine 4 monomethylation (H3K4me1) in a cancer- and cell type-specific manner.
In this resource paper, we present the genome-wide localization analysis of SRC-3 chromatin affinity sites in MCF-7 human breast cancer chromatin and compare the cis binding sites to global cartographies for ER and FoxA1.
Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer.
A conserved PR binding element was identified in PR binding regions from both cell lines, but there were distinct patterns of enrichment of known cofactor binding motifs, with FOXA1 sites over-represented in breast cancer cell binding regions and NF1 and AP-1 motifs uniquely enriched in the immortalized normal line.
This study explored the FOXA1 relationship with luminal and basal breast cancer subtypes, proliferation markers, and survival in breast cancer patients who had received similar treatment.
Stable expression of FOXA1, but not ERα, reduced the expression of <i>IL6</i> in the FOXA1- and ERα-negative breast cancer MDA-MB-231 cells and TAM-R cells, without affecting the activation of the NF-κB signaling pathways.
The analysis revealed already well-established associations with XBP1 and FOXA1, but also identified a strong association with CT62, a potential immunotherapeutic target with few previous associations with breast cancer.
Recently, a groundbreaking study by the Lupien group has shown that risk-associated SNPs of breast cancer are enriched for FOXA1 binding sites, which influences the function of this transcription factor.
Our results show that breast cancer risk-associated SNPs are enriched in the cistromes of FOXA1 and ESR1 and the epigenome of histone H3 lysine 4 monomethylation (H3K4me1) in a cancer- and cell type-specific manner.
Interdependency between these three factors in breast cancer and normal mammary development has been suggested, but the specific role for FOXA1 is not known.
The comparison of our signature with two pioneering signatures, the Sorlie's signature and PAM50, suggests a novel marker, FOXA1, in breast cancer classification.
FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding.
This is in line with other studies suggesting these SNPs as risk-associated polymorphisms which may lead to a change in the affinity of FOXA1, as a distal enhancer, to <i>TOX3</i> and thus change in <i>TOX3</i> expression, which can eventually affect the risk of breast cancer.
Here in this study, we aimed to identify which are the proteins that could potentially control FOXA1 function in breast cancer cell lines expressing different molecular markers.
In contrast, constitutive (MYC, TBX3) and signal-induced (TP53, FOXA1) DB-TFs that do not mediate default repression are directly altered in breast cancer.
Particularly, our model correctly prioritized SNPs that are proved to be enriched for the binding sites of FOXA1 in breast cancer cell lines from previous studies.