Indeed, BRCA1 has been demonstrated to regulate the signalling axis of the hormone, progesterone, and its receptor, the progesterone receptor (PR), and progesterone action has been implicated in BRCA1-related tumorigenesis.
However, recent studies not only identify new functions for BRCA1 and BRCA2 in the regulation of transcription and RNA processing potentially relevant to their tumour suppressive activity, but also suggest that monoallelic BRCA2 gene mutations suffice for carcinogenesis.
We identified one individual with a deleterious BRCA1 variant, however, this allele was lost (with the wild-type allele remaining) in the corresponding CM, indicating that defective BRCA1 was not a driver of tumorigenesis in this instance.
Our findings offer new mechanistic insights into BRCA1 mutation-associated transcriptional and epigenetic abnormality in breast epithelial cells and tissue/cell lineage-specific tumorigenesis.
The data presented here indicate that in the absence of BRCA1 germline mutations, a higher number of driver mutations are required for tumor development and that different defective processes are operating in the tumorigenesis of hereditary and sporadic TNBC in young women.
Our findings suggest that BRCA1-dependent R-loop mitigation contributes to luminal cell-specific transcription and differentiation, which could in turn suppress BRCA1-associated tumorigenesis.
Nevertheless, because SFP, unlike HDR, is also impaired in heterozygous Brca1/Bard1 mutant cells, SFP and HDR may contribute to distinct stages of tumorigenesis in BRCA1/BARD1 mutation carriers.
The present study aimed to elucidate the expression profiles, mutations and interaction networks of BRCA1 and BRCA2, which may provide insights to reveal the mechanisms of BRCA genes ultimately leading to breast or ovarian tumorigenesis.
To further understand how ZNF121 functions in cell proliferation and carcinogenesis, we identified and characterized the interaction of ZNF121 with zinc finger and BRCA1-interacting protein with a KRAB domain 1 (ZBRK1), a breast and ovarian cancer susceptibility protein 1 (BRCA1)-interacting protein, using the yeast two-hybrid assay and other approaches.
In addition, in both tumors, the wild-type BRCA1 allele was lost, indicating the inactivation of the BRCA1 gene and arguing for a link with endometrial carcinogenesis.
Together, our results illustrate that BRCA1-associated tumorigenesis is dependent on estrogen signaling rather than on progesterone signaling, and call into question the utility of PR antagonists as a tumor prevention strategy for BRCA1 mutation carriers.
Genetic ablation of Cobra1, which encodes a Pol II-pausing and BRCA1-binding protein, ameliorates R-loop accumulation and reduces tumorigenesis in Brca1-knockout mouse mammary epithelium.
In addition, clinicopathologic variables in <i>BRCA1</i>-mutated ER<sup>+</sup> cancer were also more similar to <i>BRCA2</i>-mutated ER<sup>+</sup> and sporadic ER<sup>+</sup> breast cancer than to <i>BRCA1</i>-mutated ER<sup>-</sup> cancers.<b>Conclusions:</b> As <i>BRCA1</i>-mutated ER<sup>+</sup> tumors show a BRCAness copy number profile and LOH, it is likely that the loss of a functional BRCA1 protein plays a role in tumorigenesis in <i>BRCA1</i>-mutated ER<sup>+</sup> tumors.