Ngo Thi Ha, Doan Thi Hong Van, Le Thi Thu Ha, Ta Bich Thuan, Vo Thi Thuong Lan

Main Article Content

Abstract

Abstract: DNA promoter methylation, a main way of epigenetic regulation, has been studied for detection, prognosis and treatment of breast cancer. In this study, methylation specific polymerase chain reaction (MSP) was used to analyze the promoter methylation of 2 tumor suppressor genes BRCA1 and RASSF1A in tumor and paired adjacent normal tissues of 76 Vietnamese breast cancer patients. We found that tumor and paired adjacent normal tissues were frequently hypermethylated for the two tested genes. The BRCA1 and RASSF1A were highly methylated in tumors (60.5% and 76.3%) and adjacent normal tissues (52.6% and 65.8%), respectively. Further more, there was a high agreement between BRCA1 and RASSF1A methylation in tumor and adjacent tissues (p=0.000050 and p<0.000001). But the differences between methylation in tumor and adjacent tissues were not observed with these genes. On the other hand, there was a significant association between tumor grade and BRCA1 methylation in tumor tissues (p=0.035430), but not with RASSF1A. Beside that, no significant association was observed between methylation status of the two genes and other clinicopathological factors of tumors (age, histological tumor type and metastasis status).

Keywords:  Promoter methylation, BRCA1, RASSF1A, adjacent normal tissues, breast cancer.

References

[1] J. Ferlay, I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012, International Journal of Cancer 136 (2015) E359.
[2] K. Rosenberg, Ten-year risk of false-positive screening mammograms and clinical breast examinations, The New England Journal of Medicine 338 (1998) 1089.
[3] M. Esteller, J.M. Silva, G. Dominguez, F. Bonilla, X. Matias, E. Lerma, E. Bussaglia, Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors, Journal of the National Cancer Institute 92 (2000) 564.
[4] Y.H. Cho, H. Yazici, H.C. Wu, M.B. Terry, K. Gonzalez, M. Qu, N. Dalay, R.M. Santella, Aberrant promoter hypermethylation and genomic hypomethylation in tumor, adjacent normal tissues and blood from breast cancer patients, Anticancer Research 30 (2010) 2489.
[5] M. Widschwendter, P.A. Jones, DNA methylation and breast carcinogenesis, Oncogene 21 (2002) 5462.
[6] L. Zhang, X. Long, Association of BRCA1 promoter methylation with sporadic breast cancers: Evidence from 40 studies, Scientific Reports 5 (2015) 17869.
[7] W. Yeo, W. Wong, N. Wong, B.K. Law, G.M. Tse, S. Zhong, High frequency of promoter hypermethylation of RASSF1A in tumorous and non-tumourous tissue of breast cancer, Pathology 37 (2005) 125.
[8] Q. Li, W. Wei, Y. Jiang, H. Yang, J. Liu, Promoter methylation and expression changes of BRCA1 in cancerous tissues of patients with sporadic breast cancer, Oncology Letter 9 (2015) 1807.
[9] V.T.T. Lan, T.B. Thuan, D.M. Thu, N.T. Ha, N.Q. Uyen, T.V. To, Methylation profile of BRCA1, RASSF1A and ER in Vietnamese women with ovarian cancer, Asian Pacific Journal of Cancer Prevention 14 (2013) 7713.
[10] V.T.T. Lan, N.T. Ha, N.Q. Uyen, N.T. Duong, N.T.T. Huong, T.B. Thuan, P.A.T. Duong, T.V. To, Standardization of methylation specific PCR (MSP) method for analysing BRCA1 and ER methylation, Molecular Medicine Reports, 9 (2014) 1844.
[11] J.G. Herman, J.R. Graff, S. Myohanen, B.D. Nelkin, S.B. Baylin, Methylation-specific PCR: A novel PCR assay for methylation status of CpG islands, Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 9821.
[12] N. Buyru, J. Altinisik, F. Ozdemir, S. Demokan, N. Dalay, Methylation profiles in breast cancer, Cancer Investigation 27 (2009) 307.
[13] T. Ignatov, A. Poehlmann, A. Ignatov, A. Schinlauer, S.D. Costa, A. Roessner, T. Kalinski, J. Bischoff, BRCA1 promoter methylation is a marker of better response to anthracycline-based therapy in sporadic TNBC, Breast Cancer Research and Treatment 141 (2013) 205.
[14] A. Agathanggelou et al., Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumours, Oncogene 20 (2001) 1509.
R. Dammann, G. Yang, G.P. Pfeifer, Hypermethylation of the CpG island of Ras association domain family 1A (RASSF1A), a putative tumor suppressor gene from the 3p21.3 locus, occurs in a large percentage of human breast cancers, Cancer Research 61 (2001) 3105