Version 1
: Received: 5 July 2024 / Approved: 8 July 2024 / Online: 8 July 2024 (12:33:45 CEST)
How to cite:
Kanaan, Y. Methylation of ESRα Promoters in Benign Breast Tumors Could Be a Signature for Progression into Breast Cancer in African American Women. Preprints2024, 2024070628. https://doi.org/10.20944/preprints202407.0628.v1
Kanaan, Y. Methylation of ESRα Promoters in Benign Breast Tumors Could Be a Signature for Progression into Breast Cancer in African American Women. Preprints 2024, 2024070628. https://doi.org/10.20944/preprints202407.0628.v1
Kanaan, Y. Methylation of ESRα Promoters in Benign Breast Tumors Could Be a Signature for Progression into Breast Cancer in African American Women. Preprints2024, 2024070628. https://doi.org/10.20944/preprints202407.0628.v1
APA Style
Kanaan, Y. (2024). Methylation of ESRα Promoters in Benign Breast Tumors Could Be a Signature for Progression into Breast Cancer in African American Women. Preprints. https://doi.org/10.20944/preprints202407.0628.v1
Chicago/Turabian Style
Kanaan, Y. 2024 "Methylation of ESRα Promoters in Benign Breast Tumors Could Be a Signature for Progression into Breast Cancer in African American Women" Preprints. https://doi.org/10.20944/preprints202407.0628.v1
Abstract
Methylation in the estrogen receptor alpha (ESRα) promoter is an epigenetic abnormality in breast cancer (BCa) and hypermethylation results in the loss of ER expression. We used pyrosequencing to investigate if there is a direct link between P0/P1 promoters of ESRα aberrant methylation and risk of progression of benign tumors to BCa. Results showed a significant elevated level of DNA methylation in ESRα P1 promoter (p = 0.0001) in fibroadenoma than ER-negative BCa tissues, and a 2-fold increased ESRα expression in fibrocystic, and fibroadenoma. In addition, the methylation level of HIN-1 and RASSF1A promoters were elevatedin ER-positive when compared to ER-negative BCa (p-value <0.5). ANOVA Mixed Model revealed a significant interaction between RASSF1A with fibroadenoma and ER-positive BCa (p = 0.004). Tumors with unclassified molecular subtype (ER-positive, PR-negative, HER2-negative) had elevated levels of methylation (p = 0.046) in the P0 promoter compared with luminal B (ER-positive, PR-positive, HER2-positive) tumors. Tumors with grade 3 showed a borderline association with ESRα P1 promoter methylation when compared with grade 2 tumors (p = 0.056). These results showed a highly methylated ESRαP0 promoter in the initial stages of breast carcinogenesis while the methylation in the P1 promoter occurs at later stages of BCa with poor prognosis. Therefore, methylation of ESRα promoter and tumor-related genes could serve as potential biomarker for prediction of fibroadenoma that are at elevated risk of progressing to BCa.
Keywords
DNA methylation; estrogen receptor alpha; breast cancer; fibroadenoma
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
