|تعداد مشاهده مقاله||9,731,322|
|تعداد دریافت فایل اصل مقاله||6,362,776|
Relationship between Promoter Hypermethylation of DNMT3A and DNMT3B genes and Endometrial Cancer
|Journal of Epigenetics|
|مقاله 4، دوره 1، شماره 1، اردیبهشت 2019، صفحه 19-23 اصل مقاله (815.8 K)|
|نوع مقاله: Original Article|
|شناسه دیجیتال (DOI): 10.22111/jep.2019.27203.1005|
|Masoumeh Omidali1؛ Neda Jabbara1؛ Golnaz Asaadi tehrani* 2|
|1MSc of Biology-Genetics, Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.|
|2Assistant Professor, Molecular Genetics Ph.D, Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.|
|Aberrant DNA methylation is an epigenetic event that occurs by methyltransferases. DNMT3A and DNMT3B are responsible for de novo methylation that plays important roles in normal development and disease. A number of reports on methylation of various genes in endometrial cancer have been published, but most of these studies focused on tumor suppressor genes. In this study, we determined the promoter methylation pattern of DNMT3A and DNMT3B genes; also we analyzed correlations between methylation statuses with clinicopathological parameters. 28 patients and 22 healthy controls were studied. Isolation of genomic DNA from FFPE and peripheral blood was performed and Methylation-Specific PCR (MSP) was applied for analysis the promoter CpG methylation status of DNMT3A and DNMT3Bgenes in the studied population. A significant difference was found between the study groups and the presence of promoter CpG hypermethylation status in the DNMT3A (P=0.04) gene. Furthermore methylation status between tissue and blood samples of DNMT3A genewas not significant (p=0.78). Our results indicated correlation between age and menopausal state with DNMT3B promoter methylation, but there were no significant relationships between parameters such as tumor grade, type of tumor, amount of metastasis and myometrium invasion, furthermore diabetes (p = 0.01) and obesity (p = 0.027) were two important items in endometrial cancer incidence. In our study hypermethylation of DNMT3A gene was found as an important event in carcinogenesis of endometrial cancer. The inactivation epigenetic of methylation regulation genes is a common occurrence in many cancers, including endometrial cancer.|
|Endometrial cancer؛ promoter hypermethylation؛ MSP؛ DNMT3a؛ DNMT3b|
Baylin SB. (2005) DNA methylation and gene silencing in cancer. Nat Clin Pract Oncol , 2(1):S4-11.
Covens A, Brunetto VL, Markman M, Orr JW, Jr, Lentz SS, Benda J. (2003) Phase II trial of danazol in advanced, recurrent, or persistent endometrial cancer: a Gynecologic Oncology Group Study. Gynecol Oncol , 89:470–4.
Colombo N, Preti E, Landoni F, Carinelli S, Colombo A, Marini C, et al.(2013) Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol , 24: 338.
Cheng X, Blumenthal RM.(2008) Mammalian DNA methyltransferases: a structural perspective. Structure , 16:341-50; PMID:18334209.
Chen BF and Chan WY.(2014) The de novo DNA methyltransferase DNMT3A in development and cancer. Epigenetics , 9(5):669–677.
Chédin F. (2011) The DNMT3 family of mammalian de novo DNA methyltransferases. Prog Mol Biol Transl Sci , 101:255-85; PMID:21507354.
Esteller M.(2007) Epigenetics provides a new generation of oncogenes and tumour-suppressor genes. Br J Cancer , 96:26-30; PMID:17393582
Feinberg AP and Tycko B.(2004) The history of cancer epigenetics. Nat Rev Cancer , 4: 143-153.
Gomori E, Pal J, Kovacs B, Doczi T. (2012) Concurrent hypermethylation of DNMT1, MGMT and EGFR genes in progression of gliomas. Diagn Pathol. ; 7:8–15.
Geiger TR, Peeper DS.(2009) Metastasis mechanisms. Biochim Biophys Acta , 1796(2):293–308.
Hanahan D and Weinberg RA. (2011) Hallmarks of cancer: the next generation. Cell, 144: 646-674.
Hatzimichael E and Crook T. (2013) Cancer epigenetics: new therapies and new challenges. J Drug Deliv, 13: 529312.
Kimberly K, Kristina W, Michael J, Koen De Geest, Yichen Jiae, and Shujie Yang(2012). Endometrial Cancer. Obstet Gynecol Clin North Am , 39(2): 255–268.
Kaneda M, Okano M., Hata K, Sado T, Tsujimoto N, Li E, et al.(2004) Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature , 429: 900-903.
Lee SJ, Jeon HS, Jang JS, Park SH, Lee GY, et al.(2005) DNMT3B polymorphisms and risk of primary lung cancer. Carcinogenesis, 26:403-409.
Naghitorabi M, Mohammadi Asl J , Mir Mohammad Sadeghi H,. Rabbani M, Jafarian-Dehkordi A and Haghjooye Javanmard S.(2013) Quantitative evaluation of DNMT3B promoter methylation in breast cancer patients using differential high resolution melting analysis. Research in Pharmaceutical Sciences , 8(3): 167-175.
Peralta-Arrieta I, Hernández-Sotelo D, Castro-Coronel Y, Leyva-Vázquez MA, Illades-Aguiar B. (2017) DNMT3B modulates the expression of cancer-related genes and downregulates the expression of the gene VAV3 via methylation. Am J Cancer Res , 7(1):77-87.
Roll JD, Rivenbark AG, JonesWD and Coleman WB.(2008) DNMT3b overexpression contributes to a hypermethylator phenotype in human breast cancer cell lines. Molecular Cancer , 7:15. doi:10.1186/1476-4598-7-15.
Sweet MG, Schmidt-Dalton TA, Weiss PM, Madsen KP.(2012) Evaluation and management of abnormal uterine bleeding in premenopausal women. Am Fam Physician , 85:35–43.
Smith ZD, Meissner A .(2013) DNA methylation: roles in mammalian development. Nat Rev Genet , 14: 204–220. doi: 10.1038/nrg3354 PMID: 23400093.
Suzuki MM,(2008) Bird A. DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet , 9: 465–476. doi: 10.1038/nrg2341 PMID: 18463664.
Tao MH and Freudenheim JL.(2010) DNA methylation in endometrial cancer. Epigenetics , 5: 491-498.
Teneng I, Tellez CS, Picchi MA, Klinge DM, Yingling CM, Snider AM, et al.(2015) Global identification of genes targeted by DN-MT3b for epigenetic silencing in lung cancer. Oncogene , 34: 621-630.
Widschwendter M, Jones PA.(2002) DNA methylation and breast carcinogenesis. Oncogene , 21:5462-82.
Wu Y, Strawn E, Basir Z, Halverson G, and Guo SW.(2007) Aberrant expression of deoxyribonucleic acid methyltransferases DNMT1, DNMT3A, and DNMT3B in women with endometriosis. ENDOMETRIOSIS , 87: 1. doi:10.1016/j.fertnstert.2006.05.077.
Warton K, Samimi G. (2015) Methylation of cell-free circulating DNA in the diagnosis of cancer. Front Mol Biosci, 2(13): 1-10.
Wong TS, Kwong DLW, Sham JST, Wei WI, Kwong YL and Yuen APW.(2004) Quantitative plasma hypermethylated DNA markers of undifferentiated nasopharyngeal carcinoma. Clin Cancer Res ,10: 2401–2406.
Wang J, Bhutani M, Pathak AK, Lang W, Ren H, Jelinek J,et al.(2007) Delta DNMT3B variants regulate DNA methylation in a promoter-specific manner. Cancer Res , 67: 10647-10652.
Weisenberger DJ, Velicescu M, Cheng JC, Gonzales FA, Liang G, and Jones PA.(2004) Role of the DNA Methyltransferase Variant DNMT3b3. Molecular Cancer Research , 2: 62–72.
Yeramian A, Moreno-Bueno G, Dolcet X, Catasus L, Abal M, Colas E, et al.(2013) Endometrial carcinoma: molecular alterations involved in tumor development and progression. See comment in PubMed Commons below Oncogene , 32: 403-413.
Yanagisawa Y., Ito E., Yuasa Y. and Maruyama K. (2002), The human DNA methyltransferases DNMT3A and DNMT3B have two types of promoters with different CpG contents . Biochimica et Biophysica Acta 1577 : 457 – 465.
Zhu X, Mao X, Hurren R, Schimmer AD, Ezzat S, Asa SL. (2008) Deoxyribonucleic acid methyltransferase 3B promotes epigenetic silencing through histone 3 chromatin modifications in pituitary cells. J Clin Endocrinol Metab. ;93:3610–3617.
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