BRCA1/2甲基化和表达动态在遗传性乳腺癌和卵巢癌：从基因，蛋白质和TCGA分析的见解。

IF 2.5 3区医学 Q2 ONCOLOGY

Clinical & Translational Oncology Pub Date : 2025-10-01 Epub Date: 2025-04-30 DOI:10.1007/s12094-025-03934-w

Bhoomi Tarapara, Franky Shah

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引用次数: 0

摘要

背景：BRCA1/2突变与乳腺癌和卵巢癌的遗传风险有关。然而，BRCA1和BRCA2启动子甲基化导致的基因沉默尚未得到广泛研究。材料与方法：采用甲基化特异性qPCR对113例遗传性乳腺癌和卵巢癌患者gDNA中BRCA1和BRCA2启动子甲基化进行检测。结果：大多数患者的BRCA2甲基化高于BRCA1，并且与遗传性乳腺癌和卵巢癌显著相关，而且BRCA2甲基化与BRCA2下调显著相关。此外，25名高甲基化患者的蛋白质表达分析表明，BRCA1和BRCA2的甲基化状态和蛋白质表达之间存在显著的负相关。结论：BRCA1和BRCA2启动子甲基化，特别是BRCA2，有助于基因沉默和蛋白质丢失，可能是遗传性乳腺癌和卵巢癌预后和治疗的关键生物标志物。

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BRCA1/2 methylation and expression dynamics in hereditary breast and ovarian cancer: insights from gene, protein, and TCGA analysis.

Background: BRCA1/2 Mutations have been linked to an inherited risk of breast and ovarian cancer. However, gene silencing by promoter methylation of BRCA1 and BRCA2 has not been studied extensively.

Materials and methods: Promoter methylation of BRCA1 and BRCA2 in the gDNA of 113 hereditary breast and ovarian cancer patients was carried out using methylation-specific qPCR.

Results: The majority of patients showed higher methylation in BRCA2 than in BRCA1 and were significantly associated with hereditary breast and ovarian cancer Moreover, BRCA2 methylation was significantly associated with BRCA2 downregulation. Additionally, protein expression analysis in a subset of 25 patients with hypermethylated demonstrated a significant negative correlation between methylation status and protein expression for both BRCA1 and BRCA2.

Conclusion: BRCA1 and BRCA2 promoter methylation, particularly BRCA2, contributes to gene silencing and protein loss, and may act as key biomarkers for hereditary breast and ovarian cancer prognosis and therapy.

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来源期刊

Clinical & Translational Oncology 医学-肿瘤学

CiteScore

6.20

自引率

2.90%

发文量

240

审稿时长

1 months

期刊介绍： Clinical and Translational Oncology is an international journal devoted to fostering interaction between experimental and clinical oncology. It covers all aspects of research on cancer, from the more basic discoveries dealing with both cell and molecular biology of tumour cells, to the most advanced clinical assays of conventional and new drugs. In addition, the journal has a strong commitment to facilitating the transfer of knowledge from the basic laboratory to the clinical practice, with the publication of educational series devoted to closing the gap between molecular and clinical oncologists. Molecular biology of tumours, identification of new targets for cancer therapy, and new technologies for research and treatment of cancer are the major themes covered by the educational series. Full research articles on a broad spectrum of subjects, including the molecular and cellular bases of disease, aetiology, pathophysiology, pathology, epidemiology, clinical features, and the diagnosis, prognosis and treatment of cancer, will be considered for publication.