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Anticancer activity was observed in BC and OC and in gBRCAm (BRCA1 or BRCA2 (显示 BRCA2 蛋白))and gBRCA wild-type (gBRCAwt) patient. BKM120 and olaparib can be co-administered, but the combination requires attenuation of the BKM120 dose. Clinical benefit was observed in both gBRCAm and gBRCAwt pts (显示 PTS 蛋白).
Data indicate there was high genetic correlation between risk of estrogen receptor (ER (显示 ESR1 蛋白))-negative breast cancer and breast cancer risk for BRCA1 mutation carriers.
BRCA1 was methylated in 9.33% of breast tumors and was associated with lymphatic metastasis.
Our results provide novel insights regarding the physician-patient interaction and the organizational aspects of the health-care system that may significantly impact the cancer screening practices of BRCA1/2 noncarriers.
Germline BRCA1/2 gene mutations could result in genomic instability and an elevated gene mutation rate (such as the p53 (显示 TP53 蛋白) gene) in breast luminal cells compared with the general population, predisposing BRCA carriers to develop p53 (显示 TP53 蛋白)-positive/triple-negative breast carcinomas.
Data suggest that locus-specific LOH may be a clinically useful biomarker to predict primary resistance to DNA damaging agents in patients with germline BRCA1 and BRCA2 (显示 BRCA2 蛋白) mutations.
Our findings suggest that BRCA1 exons 1-2 deletion and exons 21-24 deletion should be included in the recurrent BRCA1/2 mutations panel for genetic testing of high-risk Pakistani breast/ovarian cancer patients.
we saw no increased risk of cardiotoxicity among breast cancer patients with BRCA1 and/or BRCA2 (显示 BRCA2 蛋白) gene mutations treated with standard doses of anthracycline compared to the general population.
This is the largest study of comprehensive BRCA testing(BRCA1 and BRCA2 (显示 BRCA2 蛋白)) among Brazilians to date. Several criteria that are not included in the NCCN achieved a higher predictive value. Identification of the most informative criteria for each population will assist in the development of a rational approach to genetic testing
Data show a consistent NFkappaB hyperactivity associated with BRCA1 dysfunction as a consequence of increased reactive oxygen species (ROS) in a subset of BRCA1-mutant and triple negative breast cancer.
Investigation on BRCA1 SNPs and its effects on mastitis in Chinese commercial cattle.
The gene-specific SNP marker analysis showed a significant association of BRCA1 C28300A with milk somatic cell scores.
In general, OC use, childbearing and breastfeeding do not differ between BRCA1/2 carriers and non-carriers with ovarian cancer. However, the effects of tubal ligation may differ between BRCA1 carriers and non-carriers.
Bovine BRCA1 was phosphorylated and nuclear speckling was enhanced in response to DNA-damaging agents.These results provide evidence that phosphorylation and nuclear relocalization are highly conserved features of the BRCA1 response to genotoxic stress.
Consensus-based recombinant adeno-associated virus-BRCA1 knock out virus vectors failed to induce BRCA1 knockout in Gottingen fibroblasts.
Brca1 is necessary for hematopoietic stem cells maintenance and normal hematopoiesis and that distinct mutations lead to different degrees of hematopoietic dysfunction.
TGFbeta (显示 TGFB1 蛋白) stabilized the abundance of BRCA1 by reducing the abundance of microRNA-182 (miR (显示 MLXIP 蛋白)-182). Ectopic expression of BRCA1 or antagonism of miR (显示 MLXIP 蛋白)-182 in cultured TGFbeta (显示 TGFB1 蛋白)-deficient mammary epithelial cells restored luminal lineage commitment.
BRCA1 inactivation can increase expression of miR (显示 MLXIP 蛋白)-155, contributing to cardiac hypertrophy. And Rev produces their beneficial effects partially by down-regulating miR (显示 MLXIP 蛋白)-155 expression, which might be a novel strategy for treatment of cardiac hypertrophy.
both murine Brca1185stop tumors and human BRCA1185delAG breast cancer cells express a new gene domain-less (RING-less) BRCA1 protein that mediated resistance to homologous recombination deficient-targeted therapies
Genomic instability can be rescued by deletion of Trp53bp1 (显示 TP53BP1 蛋白), encoding the DNA damage response factor 53BP1 (显示 TP53BP1 蛋白); mice expressing RING-less BRCA1 do not show an increased susceptibility to tumors in the absence of 53BP1 (显示 TP53BP1 蛋白); Genomic instability in cells expressing RING-less BRCA1 correlates with loss of BARD1 (显示 BARD1 蛋白) and a defect in restart of replication forks after hydroxyurea treatment
the aberrant proliferative capacity of Brca1(-/-) luminal progenitor cells is linked to the replication-associated DNA damage response, where proliferation of mammary progenitors is perpetuated by damage-induced, autologous NF-kappaB (显示 NFKB1 蛋白) signaling.
We report here elevated recombination rates at telomeres in cells from human BRCA1 mutation carriers and in mouse embryonic stem cells lacking both copies of functional Brca1.
loss of Brca1, a tumor suppressor that functions in DNA damage repair, in the mammary epithelium induced senescence with induction of p16 and a decline of stem cell function, which was rescued by p16 loss.
Brca1-Wwox (显示 WWOX 蛋白) interaction supports non-homologous end-joining as the dominant DSB repair pathway in Wwox (显示 WWOX 蛋白)-sufficient cells
Structure-guided separation-of-function mutations show that the RNF8 E2 stimulating activity is essential for DSB signaling in mammalian cells and is necessary for downstream recruitment of 53BP1 and BRCA1.
MRN (Mre11 (显示 MRE11A 蛋白), Rad50 (显示 RAD50 蛋白), and Nbs1 (显示 NLRP2 蛋白)) complex, CtIP (显示 RBBP8 蛋白), and BRCA1 are required for both the removal of Top2 (显示 TOP2 蛋白)-DNA adducts and the subsequent resection of Top2 (显示 TOP2 蛋白)-adducted DSB ends.
BRCA1-dependent helicase unloading is a critical, early event in DNA interstrand crosslink repair.
This gene encodes a nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified.
BRCA1/BRCA2-containing complex, subunit 1
, RING finger protein 53
, breast and ovarian cancer susceptibility protein 1
, breast and ovarian cancer sususceptibility protein 1
, breast cancer type 1 susceptibility protein
, protein phosphatase 1, regulatory subunit 53
, BRCA1 homologue
, breast cancer type 1 susceptibility protein homolog
, breast cancer 1, early onset
, BRCA1 homolog
, breast and ovarian cancer susceptibility protein
, breast cancer associated 1