Prevalence of BRCA1 and BRCA2 genes promoter hypermethylation in breast cancer tissue
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-43-no-1.15703Keywords:
BRCA1, BRCA2, breast cancer, hypermethylation, promoterAbstract
Background: Recent advances in the treatment of breast cancer (BC) have been related to the personalization of therapy. The methylation status of the promoter regions of tumor suppressor genes such as BRCA1 and BRCA2 is supposed to be useful as a prognostic factor in BC patients. Aim: To investigate the frequency of hypermethylation in the promoter regions of BRCA1 and BRCA2 genes in tumor tissue of BC patients, and the relation of hypermethylation to the clinical course of the disease. Materials and Methods: Molecular genetic studies were performed on 50 BC tissue samples in order to determine the methylation status of the promoter regions of the BRCA1 and BRCA2 genes. Results: Hypermethylation of the BRCA1 promoter region was detected in 34% of BC cases, hypermethylation of the BRCA2 promoter region — in 50% of cases, and hypermethylation of the promoter region of both genes — in 20% of cases. A significant increase in the incidence of hypermethylation of the BRCA2 promoter region was found in the group of patients older than 56 years, mainly in patients with triple-negative breast cancer and without family history of BC. Conclusions: The high frequency of hypermethylation in the promoter regions of BRCA1 and BRCA2 genes, as well as their co-methylation in tumor tissue of BC patients has been detected.
References
Kanwal R, Gupta S. Epigenetic modifications in cancer. Clinical Genetics 2012; 81: 303–11.
Chen RZ, Pettersson U, Beard C, et al. DNA hypomethylation leads to elevated mutation rates. Nature 1998; 395: 89–93.
Terry MB, Delgado-Cruzata L, Vin-Raviv N, et al. DNA methylation in white blood cells: Association with risk factors in epidemiologic studies. Epigenetics 2011; 6: 828–37.
Stein RA. DNA methylation profiling: a promising tool and a long road ahead for clinical applications. Int J Clin Pract 2011; 65: 1212–3.
Williams SCP. Epigenetics. Proc Natl Acad Sci USA 2013; 110: 3209.
Ehrlich M. DNA hypermethylation in disease: mechanisms and clinical relevance. Epigenetics 2019; 14: 1141–63.
Meisel JL, Hyman DM, Garg K, et al. The performance of BRCA1 immunohistochemistry for detecting germline, somatic, and epigenetic BRCA1 loss in high-grade serous ovarian cancer. Ann Oncol 2014; 25: 2372–8.
Pennington KP, Walsh T, Harrell MI, et al. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res 2014; 20: 764–75.
Ibragimova I, Cairns P. Assays for hypermethylation of the BRCA1 gene promoter in tumor cells to predict sensitivity to PARP-Inhibitor therapy. Methods Mol Biol 2011; 780: 277–91.
Fouad MA, Salem SE, Hussein MM, et al. Impact of global DNA methylation in treatment outcome of colorectal cancer patients. Front Pharmacol 2018; 9: 1–14.
Yang D, Khan S, Sun Y, et al. Association between BRCA2 but not BRCA1 mutations and beneficial survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA 2011; 306: 1557–65.
Darehdori AS, Dastjerdi MN, Dahim H, et al. Lack of significance of the BRCA2 promoter methylation status in different genotypes of the MTHFR a1298c polymorphism in ovarian cancer cases in Iran. Asian Pacific J Cancer Prev 2012; 13: 1833–6.
Franzese E, Centonze S, Diana A, et al. Genomic profile and BRCA-1 promoter methylation status in BRCA mutated ovarian cancer: new insights in predictive biomarkers of olaparib response. Front Oncol 2019; 9: 1289.
Stefansson OA, Villanueva A, Vidal A, et al. M. BRCA1 epigenetic inactivation predicts sensitivity to platinum-based chemotherapy in breast and ovarian cancer. Epigenetics 2012; 7: 1225–9.
Staaf J, Glodzik D, Bosch A, et al. Europe PMC Funders Group Whole-genome-sequencing of triple negative breast cancers in a population-based clinical study. Nat Med 2019; 25: 1526–33.
Stordal B, Timms K, Farrelly A, et al. BRCA1/2 mutation analysis in 41 ovarian cell lines reveals only one functionally deleterious BRCA1 mutation. Mol Oncol 2013; 7: 567–79.
Kondrashova O, Topp M, Nesic K, et al. Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma. Nat Commun 2018; 9: 3970.
Shchepotin NB, Ganul VL, Bondar GV. Standards for diagnosis and treatment of cancer patients. Kyiv, 2007. 199 p. (in Ukrainian).
Telli ML, Gradishar WJ, Ward JH. NCCN Guidelines Updates: Breast Cancer. J Natl Compr Canc Netw 2019; 17: 552–5.
Cardoso F, Kyriakides S, Ohno S, et al. Early Breast Cancer: ESMO Clinical Practice Guidelines. Ann Oncol 2019; 30: 1194–220.
Xu Y, Diao L, Chen Y, et al. Promoter methylation of BRCA1 in triple-negative breast cancer predicts sensitivity to adjuvant chemotherapy. Ann Oncol 2013; 24: 1498–505.
Joosse SA, Brandwijk KI, Mulder L, et al. Genomic signature of BRCA1 deficiency in sporadic basal-like breast tumors. Genes Chromosomes Cancer 2011; 50: 71–81.
Tabano S, Azzollini J, Pesenti C, et al. Analysis of BRCA1 and RAD51C promoter methylation in italian families at high-risk of breast and ovarian cancer. Cancers (Basel) 2020; 12: 1–8.
Bosviel R, Garcia S, Lavediaux G, et al. BRCA1 promoter methylation in peripheral blood DNA was identified in sporadic breast cancer and controls. Cancer Epidemiol 2012; 36: 177–82.
Medvedieva N, Lobanova O, Rossokha Z, et al. Methylation status in promoter region of RUNX3 gene among woman with breast cancer depending of age. Exp Oncol 2019; 41: 272–3.
Salameh Y, Bejaoui Y, El Hajj N. DNA methylation biomarkers in aging and age-related diseases. Front Genet 2020; 11: 171.
Grybach SМ. Features of the somatic status and clinical characteristics of breast cancer in postmenopausal women. Reproductive Endocrinology 2018; 42: 76–81 (in Russian).
Bosviel R, Durif J, Guo J, et al. BRCA2 promoter hypermethylation in sporadic breast cancer. Omi A J Integr Biol 2012; 16: 707–10.
Vos S, Moelans CB, van Diest PJ. BRCA promoter methylation in sporadic versus BRCA germline mutation-related breast cancers. Breast Cancer Res 2017; 19: 1–13.
Watanabe Y, Maeda I, Oikawa R, et al. Aberrant DNA methylation status of DNA repair genes in breast cancer treated with neoadjuvant chemotherapy. Genes to Cells 2013; 18: 1120–30.
Foedermayr M, Sebesta M, Rudas M, et al. BRCA1 methylation and TP53 mutation in triple-negative breast cancer patients without pathological complete response to taxane-based neoadjuvant chemotherapy. Cancer Chemother Pharmacol 2014; 73: 771–8.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Experimental Oncology
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
