The high methylation level of a novel 151-bp CpG island in the ESR1 gene promoter is associated with a poor breast cancer prognosis

Abstract

Background The ESR1 gene suffers methylation changes in many types of cancers, including breast cancer (BC), the most frequently diagnosed cancer in women that is also present in men. Methylation at promoter A of ESR1 is the worse prognosis in terms of overall survival; thus, the early detection, prognostic, and prediction of therapy involve some methylation biomarkers. Methods Therefore, our study aimed to examine the methylation levels at the ESR1 gene in samples from Mexican BC patients and its possible association with menopausal status. Results We identified a novel 151-bp CpG island in the promoter A of the ESR1 gene. Interestingly, methylation levels at this CpG island in positive ERα tumors were approximately 50% less than negative ERα or control samples. Furthermore, methylation levels at ESR1 were associated with menopausal status. In postmenopausal patients, the methylation levels were 1.5-fold higher than in premenopausal patients. Finally, according to tumor malignancy, triple-negative cancer subtypes had higher ESR1 methylation levels than luminal/HER2+ or luminal A subtypes. Conclusions Our findings suggest that methylation at this novel CpG island might be a promising prognosis marker

14-3-3τ drives estrogen receptor loss via ERα36 induction and GATA3 inhibition in breast cancer

“…We did not see an increase in ERα66 protein levels by GATA3 overexpression. This is likely due to DNA methylation at this locus, a common characteristic in TNBC ( 38 , 39 ). Indeed, the promoter of ESR1 gene in MDA-MB-468 is hypermethylated according to the Cancer Cell Line Encyclopedia (CCLE) database ( 40 ).…”

Overexpression of Estrogen Receptor 1 (ESR-1) in metastatic prostate cancer

“…The primer sequences for the ESR1 unmethylated sequences (U) were the following: forward primer 5′-GATTGTATTTGTTTTTGTTGGGTT -3′ and reverse primer 5′-AACCAACAAACCACCTAAAAAA A-3′. 24…”