Breast tumors from BRCA1 mutation carriers are predominantly of basal subtype (i.e., triple negative), and BRCA2 mutation carriers are of luminal subtype (i.e., estrogen receptor positive).
Breast tumors (n = 3) from patients with a proven BRCA1 germline mutation also showed a significant relationship with numerical centrosome aberration (P = 0.011).
Breast tumors deficient in BRCA1 are mostly associated with basal-like breast cancers and targeted therapeutics for this disease subtype are still lacking.
Breast tumours from BRCA1 and BRCA2 mutation carriers are genetically instable and display specific patterns of chromosomal aberrations, suggestive of distinct genetic pathways in tumour progression.
BRCA1-regulated genes associated with breast tumorigenesis included the estrogen-responsive genes MYC and cyclin D1, which are overexpressed in many breast tumors; STAT1 and JAK1, key components of the cytokine signal transduction pathway; the extracellular matrix protein laminin 3A; ID4, an inhibitor of DNA-binding transcriptional activators, which in turn negatively regulates BRCA1 expression; and the prohormone stanniocalcin, expression of which is lost in breast tumor cells.
BRCA1 protein was much less expressed in breast tumour tissue from patients with the 5' UTR mutation than in samples from patients without the mutation.
BRCA1 protein was much less expressed in breast tumour tissue from patients with the 5' UTR mutation than in samples from patients without the mutation.
BRCA1 promoter methylation has also been observed in sporadic ovarian and breast tumors; however, BRCA2 promoter methylation has not been reported in sporadic tumors.
A novel tricomplex of BRCA1, Nmi, and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer.
A statistically significantly higher frequency of p53 mutations was found in breast tumors from carriers of BRCA1 mutations than from noncarriers, which adds to the accumulating evidence that loss of p53 function is an important step in the molecular pathogenesis of BRCA1 mutation-associated breast tumors.
A total of 104 tumor tissue samples from 75 familial breast tumors (BRCA1, n = 14; BRCA2, n = 13; non-BRCA1/2, n = 48) and 29 sporadic tumors were analyzed.
Aberrant promoter hypermethylation of PALB2 is more frequent than the reported level of PALB2 point mutations in breast tumors from BRCA1/2-negative families and is similar to the frequency of BRCA1 hypermethylation in inherited and sporadic breast and ovarian cancers.
Abnormalities in X chromosome copy number and in the epigenetic stability of the inactive X chromosome (Xi) have been proposed to characterize BRCA1breast tumors.