Development of high‑resolution melting analysis for ABCB1 promoter methylation: Clinical consequences in breast and ovarian carcinoma
Language English Country Greece Media print-electronic
Document type Journal Article
PubMed
31173253
DOI
10.3892/or.2019.7186
Knihovny.cz E-resources
- MeSH
- Nucleic Acid Denaturation MeSH
- Carcinoma, Ductal, Breast drug therapy genetics pathology MeSH
- Epigenesis, Genetic MeSH
- Neoplasm Invasiveness MeSH
- Humans MeSH
- DNA Methylation * MeSH
- Survival Rate MeSH
- Biomarkers, Tumor genetics MeSH
- Breast Neoplasms drug therapy genetics pathology MeSH
- Ovarian Neoplasms drug therapy genetics pathology MeSH
- Follow-Up Studies MeSH
- ATP Binding Cassette Transporter, Subfamily B genetics MeSH
- Polymerase Chain Reaction methods MeSH
- Prognosis MeSH
- Promoter Regions, Genetic * MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Retrospective Studies MeSH
- Cystadenocarcinoma, Serous drug therapy genetics pathology MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- ABCB1 protein, human MeSH Browser
- Biomarkers, Tumor MeSH
- ATP Binding Cassette Transporter, Subfamily B MeSH
Multidrug resistance to anticancer drugs, which is often associated with enhanced expression of the ATP‑binding cassette (ABC) transporter P‑glycoprotein (encoded by the ABCB1 gene) may limit the effects of cancer therapy. Epigenetic regulation of ABCB1 expression may thus have a clinical impact. A detailed assessment of ABCB1 promoter methylation is of importance for predicting therapy outcome and prognosis. Thus, validated methods for the analysis of ABCB1 promoter methylation are urgently required. In the present study, high‑resolution melting (HRM) analysis of the CpG island regions covering the distal promoter of the ABCB1 gene was developed and compared with pyrosequencing. In addition, the clinical effects of the methylation status of the ABCB1 promoter were analyzed in patients with breast and ovarian carcinoma prior and subsequent to chemotherapy treatment. HRM analysis of ABCB1 methylation correlated with the results of pyrosequencing (P=0.001) demonstrating its analytical validity and utility. Hypermethylation of the analyzed ABCB1 promoter region was significantly correlated with low levels of the ABCB1 transcript in tumors from a subset of patients with breast and ovarian carcinoma prior to chemotherapy but not following treatment. Finally, high ABCB1 transcript levels were observed in tumors of patients with short progression‑free survival prior to chemotherapy. Our data suggest the existence of functional epigenetic changes in the ABCB1 gene with prognostic value in tumor tissues of patients with breast and ovarian carcinoma. The clinical importance of such changes should be further evaluated.
References provided by Crossref.org
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