Indian Journal of Medical Biochemistry

Register      Login

VOLUME 22 , ISSUE 2 ( July-December, 2018 ) > List of Articles

ORIGINAL ARTICLE

SOX17 and RASSAF1A Promoters Methylation in Circulation Tumor Cell and Cell Free Deoxyribonucleic Acid Isolated from Plasma in Breast Cancer

Ferdous A Jabir, Sundus K Hamzah

Keywords : Breast cancer, Cell-free deoxyribonucleic acid (DNA) Methylation, RASSAF1A gene, SOX17 gene.

Citation Information : Jabir FA, Hamzah SK. SOX17 and RASSAF1A Promoters Methylation in Circulation Tumor Cell and Cell Free Deoxyribonucleic Acid Isolated from Plasma in Breast Cancer. Indian J Med Biochem 2018; 22 (2):108-113.

DOI: 10.5005/jp-journals-10054-0066

License: CC BY-NC 3.0

Published Online: 01-06-2018

Copyright Statement:  Copyright © 2018; The Author(s).


Abstract

Purpose: The study was to evaluate SOX17, and RASSEF 1A promoters methylation levels in patients with malignant breast tumors compared with healthy women. Materials and methods: Fifty women with breast cancer (range 26 to 75 years) were included in this study. They were admitted at Al-Diwaniyah Teaching Hospital, Iraq, compared with 25 women as the control. We obtained plasma samples from 50 patients (breast cancer) stages II, III, IV and normal (healthy women). Cell-free deoxyribonucleic acid (DNA) (cfDNA) extracted and methylation analysis for SOX17 and RASSEF1A gene. Results: We found different methylation pattern of the RASSEF1A gene in plasma samples between patients with breast cancer and control (p < 0.05) ranging in all cases 30 (60%) and unmethylation in 20 (40%), hyper methylation frequency in all studied cases [13 (44.8%) for II stage, 12 (80%) III stage and 4 (66.6%) IV stage of breast cancer in this study association between the hypermethylation was significant with age. 50 11.4 (71.2%) and < 50 26 (76%)] than normal cases, we found different methylation pattern of the SOX17 gene in plasma samples between patients with breast cancer and control (p < 0.05) ranging in all cases 29 (58%) and unmethylation in 21 (42%),hyper methylation frequency in all studied cases 11 (37.9%) for II stage, 13 (86.6%) III stage and 5 (83.3%) IV stage of breast cancer in this study association between the hyper methylation was significant with age (. 50 13 (81.2%) and < 50 23 (67%) than normal cases also this study association between the hypermethylation was significant with menopause (premenopause 6 (66%), post menopause 31 (75.6%) than the control group (0%). Conclusions: Our data indicate that methylation of the RASSAF1A and SOX17 genes are the frequent event in primary breast cancer and that it plays a major role in the silencing of the expression of this gene during tumor development.


PDF Share
  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources methods and major .patterns in In J Cancer 2015;136(5):E359-386.
  2. Siegel R, Naishadham D, Jemal A. Cancer statistics CA Cancer. J Clin 2013;63(1):11–30.
  3. Qiuqiong T, Jie C, Xue C, Harald S and, Barbara B. Blood-based DNA methylation as biomarker for breast cancer a systematic review. Clinical Epigenetics. 2016;8:115.
  4. Hodgson DR, Wellings R, Orr MC, Cormack R, Malone M, Board RE, et al. Circulating tumor–derived predictive biomarkers in oncology: Drug Discover 2009;15:98-101.
  5. Fleischer Hacker M, Schmidt B. Circulating nucleic acids (CNAs) and cancer asurvey Biochem Biophysics. Acta 2006;1775:181-232.
  6. Jung K, Fleisch Hacker M, Rabien A. Cell-free DNA in the blood as a solid tumor biomarker–a critical appraisal of the literature. Clin Chem Act 2010;411:1611-1624.
  7. Francesca S, Claudio O, Daniela M, Vincen zo De G, Marta G, Mario P, et al. Tumor-Related Methylated Cell–Free DNA and Circulating Tumor Cells in Melanoma. Published 2016 Jan;8.
  8. Goldberg AD, Allis CD, Bernstein E. Epigenetics: A landscape takes shape Cell 2007;128:635-638.
  9. Jones PA. Functions of DNA methylation: Islands start sites gene bodies and beyond. Nat Rev Genet 2012;13:484-492.
  10. Maunakea AK, Nagarajan RP, Bilenky M, Ballinger TJ, D'Souza C, Fouse SD, et al. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature 2010;466:253-257.
  11. Rauch TA, Wu X, Zhong X, Riggs AD Pfeifer GP. A human B cell methyl me at100-base pair resolution. Proc Natl Acad Sci USA 2009;106:671-678.
  12. Ehrlich M. DNA hypo methylation in cancer cells. Epi genomics 2009;1:239-259.
  13. Egger G, Liang G, Aparicio A, Jones, PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004; 429:457-463.
  14. Schulz WA, Dokun OY. DNA methylation and human diseases: An overview In DNA and RNA Modification Enzymes: Structure Mechanism Function and Evolution. Bioscience Austin TX USA 2009:103-116.
  15. Donninger H, Clark J, Rinaldo F, Nelson N, Barnoud T, Schmidt ML. The RASSF1A tumor suppressor regulates XPAmediated DNA repair. Mol Cell Biol 2015;35:277-287.
  16. Agostini M, Enzo MV, Bedin C, Belardinelli V, Gold in E, Del Bianca P, et al. Circulating cell-free DNA: a promising marker of regional lymph node metastasis in breast cancer patients. Cancer Bio mark 2012;11:89-98.
  17. Tanemura A, Terando AM, Sim MS, van Hoesel AQ, Maat MF, Morton DL, et al. CpG island methylate or phenol type predicts progression of malignant melanoma. Clin Cancer Res 2009;15:1801-1807.
  18. Marini A, Mirmohammad Sadegh A, Nambiar S, Gustrau A, Ruzicka T, Hengge UR. Epigenetic in activation of tumor suppressor genes in serum of patients with cutaneous melanoma. J Invest Demerol 2006;126:422-431.
  19. Koyanagi K, Mori TO’ Day SJ, Martinez SR, Hoorn DS. Association of circulating tumor cells with serum tumor-related methylated DNA in peripheral blood of melanoma patients. Cancer Res 2006;66:6111-6117.
  20. Roddick S, Mihalcioiu C, Salah RR. Detection methods of circulating tumor cells in cutaneous melanoma: a systematic review Crist Rev On col Hematology 2014;91:74-92.
  21. Sinner D, Rankin S, Lee M, Zorn AM. Sox17 and -catenin cooperate to regulate the transcription of endodermal genes. Development. 2004 Jul 1;131(13):3069-3080.
  22. Engert S, Burtscher I, Liao WP, Dulev S, Schotta G, Lickert H. Wnt/ -catenin signalling regulates Sox17 expression and is essential for organizer and endoderm formation in the mouse. Development. 2013 Jan 1:dev-088765.
  23. Li-Jin C, Wiping S, Xiaotian M, et al. SOX17 regulates the Want-beta-catenin signaling pathway in oligodendrocyte progenitor cells. J Neurosis 2011;31:13921-13935
  24. Liu Y, Asakura M, Inoue H, Nakamura T, Sano M, Niu Z, et al. Sox17 is essential for the specification of cardiac mesoderm in embryonic stem cells. Proceedings of the National Academy of Sciences. 2007 Mar 6;104(10):3859-3864.
  25. Kuok IY, Wu CC, Chang JM, et al. Low SOX17 expression is a prognostic factor and drives transcriptional dyes regulation and esophageal cancer progression. In J Cancer 2014;135:563-573
  26. Balgkouranidou, Karayiannakis A, Matthias D. Assessment of SOX17 DNA methylation in cell free DNA from patients with operable gastric cancer. Association with prognostic variables and survival Clin Chem Lab Med. 2013;51:1505-1510.
  27. Deyuan F, Chuanli R, Haosheng T. SOX17 Promoter Methylation in Plasma DNA Is Associated With Poor Survival and Can Be Used as a Prognostic Factor in Breast Cancer 2015 Mar;11(94).
  28. Ehrlich M, Gama-Sosa MA, Huang LH, Midgett RM, Kuo KC, McCune RA, Gehrke C: Amount and distribution of 5 methyl cytosine in human DNA from different types of tissues of cells. Nucleic Acids Res 1982;10: 2709-2721.
  29. Jung K, Fleischhacker M, and Rabien A. Cell-free DNA in the blood as a solid tumor biomarker–a critical appraisal of the literature. Clin Chim Acta. 2010;411:1611-1624.
  30. Madic J, Kiialainen A, Bidard FC, Birzele F, Ramey G, Leroy Q. Circulating tumor DNA and circulating tumor cells in metastatic triple negative breast cancer patients. IntJ.Cancer.2015; 136:2158-2165.
  31. Kim MS, Lee J, Sidransky D. DNA methylation markers in colorectal cancer. Cancer Metastasis Rev 2010;29:181-206.
  32. Dammann R, Schagdarsurengin U, Strunnikova M, Rastetter M, Seidel C, Liu L, et al. Epigenetic inactivation of the Ras-association domain family 1 (RASSF1A) gene and its function in human carcinogenesis. Histol Histopathol 2003;18: 665-677.
  33. Yoon JH, Dammann R, Pfeifer GP. Hyper methylation of the CpG island of the RASSF1A gene in ovarian and renal cell carcinomas. Int J Cancer 2001;94:212-217.
  34. Wagner KJ, Cooper WN, Grundy RG, Caldwell G, Jones C, Wadey RB, Morton D, Schofield PN, Reik W, Latif F, Maher ER. Frequent RASSF1A tumor suppressor gene promoter methylation in Wilms’ tumor and colorectal cancer. Oncogene 2002;21: 7277-7282.
  35. Wei-Wei Z, Lun-De Z, Gao-Xiang W, Xiao-Chun K. Promoter methylation and expression of RASSF1A genes as predictors of disease progression in colorectal cancer. 2016;9(2):2027- 2036
  36. Chimonidou M, Strati A, Tzitzira A, Sotiropoulou G, Malamos N, Georgoulias V et al. DNA methylation of tumor suppressor and metastasis suppressor genes in circulating tumor cells. Clin Chem 2011;57:1169-1177.
  37. Maria C, Areti S, Nikos M, Vasilis G, and Evi S. Lianidou. SOX17 Promoter Methylation in Circulating Tumor Cells and Matched Cell-Free DNA Isolated from Plasma of Patients with Breast Cancer. 2013.
  38. Deyuan F, Chuanli R, Haosheng T, Jinli W, Yuxiang Z. SOX17 Promoter Methylation in Plasma DNA Is Associated With Poor Survival and Can Be Used as a Prognostic Factor in Breast Cancer 2015 Feb;18.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.