In summary, data from two independent study populations showed two intronic variants in GATA3 associated with overall decreases in breast cancer risk and suggested heterogeneity of these associations by ER status.
Depletion of SCAI reduces both the accumulation of HDR factors, including BRCA1 (breast cancer susceptibility gene 1), at damage sites and the efficiency of HDR, as detected by a reporter assay system.
It has become apparent that there are very few highly recurrently mutated genes such as TP53, PIK3CA, and GATA3, that no two breast cancers display an identical repertoire of somatic genetic alterations at base-pair resolution and that there might not be a single highly recurrently mutated gene that defines each of the "intrinsic" subtypes of breast cancer (ie, basal-like, HER2-enriched, luminal A, and luminal B).
We conclude that there is no evidence that either GATA3rs570613, or any variant in strong linkage disequilibrium with it, is associated with breast cancer risk in women.
Heterozygous GATA3 mutations occur in up to 15% of estrogen receptor (ER)-positive breast tumors and have been proposed to be null alleles resulting in haploinsufficiency; however, the mutation spectrum of GATA3 in breast cancer is in sharp contrast to that found in HDR syndrome, a true GATA3 haploinsufficiency disease.
Our findings demonstrate that women who carry 17-CT (OR = 0.5; p = 0.003) or 18-CT (OR = 0.41, p = 0.02) alleles of GATA3 gene are at lower risk of developing breast cancer.
GATA3 mutations mainly occur in patients with luminal-like breast cancer and have identifiable clinicopathologic and genetic characteristics, highlighting a subgroup of patients with breast cancer in whom limited therapy may be appropriate.
To elucidate the contribution(s) of GATA3 alterations to cancer, we studied two breast cancer cell lines, MCF7, which carries a heterozygous frameshift mutation in the second zinc finger of GATA3, and T47D, wild-type at this locus.
Our findings reveal important insights into mutant GATA3 function and breast cancer, provide the first potential therapeutic strategy and suggest that dual tumour suppressive and oncogenic activities are more widespread than previously appreciated.
Our results indicate that ERα, FOXA1 and GATA3 contribute to the regulation of breast cancer susceptibility genes, which is consistent with the effects of anti-oestrogen treatment in breast cancer prevention, and suggest that fibroblast growth factor receptor 2 signalling has an important role in mediating breast cancer risk.
Through this study, we identified possible GATA3-correlated genes and core pathways that play an important role, which requires further investigation in breast cancer.
The genes that are potentially regulated by miR-206 in the mammary epithelium and/or mesenchyme, such as Tachykinin1 and Gata3, are known to be breast cancer markers.
GATA3 has been reported as a specific urothelial marker among organs in the pelvic region, and has been classified as highly sensitive and specific for urothelial and breast carcinomas.
Spread of poorly cohesive tumor cells in the gastric mucosa observed upon hematoxylin and eosin stain resembled signet ring cell carcinoma, but diffuse positive staining for GATA3 in immunohistochemical stain allowed for a conclusive diagnosis of breast cancer metastasizing to the stomach.
We propose the careful selection of GATA3 for identifying hormone receptor negativity of breast cancer, especially in the case of triple-negative breast cancer.
Even though GATA3 expression has been reported in many benign and malignant adnexal tumors (mostly of sebaceous, follicular, and apocrine differentiation), as well as in many other neoplasms, GATA3 staining to differentiate PCACC from skin breast cancer metastasis has a high negative predictive value.
Our results highlight the role of estrogen-signaling pathways (mainly CYP19/aromatase, GATA3, and ER-beta) in the risk of locoregional recurrence of breast cancer in young women.
Kaplan-Meier survival analyses showed that ER+/progesterone receptor (PgR)+ and lower grade BC patients with relatively high GATA3 had better clinical overall survival (OS).