Erişkin ve Çocukluk Cağı AML Oluşumunda ER, SOCS1, p15, E-cadherin ve RARB Promoter Metilasyonu Metilatör Fenotip Üyesi Olmaya Aday genlerdir ve Metilasyondan DNMT 3A Başlıca Sorumlu Enzim Olarak Ön Plana Çıkmaktadır

Abstract

Amaç: Hipermetilatör fenotipi, hem akut miyeloid lösemi (AML)
hem de diğer tümörler için bir terim olarak kullanılır. On genin
metilasyon durumlarını analiz ettik (DAP-kinaz, SOCS1, ER, p15,
Ecadherin, RARβ, p16, GSTP1, HIC1 ve p73) ve bunları DNA metil
transferazların (DNMT’ler) ifadesiyle korele ettik.
Gereç ve Yöntem: 25 pediatrik ve 25 yetişkin AML örneğinde metilasyon spesifik PCR ve COBRA ve DNMT’lerin (DNMT 1, 3A ve 3B)
ekspresyonunu kullanarak metilasyon profillerini analiz ettik.
Bulgular: ER, SOCS1, p15, E cadherin ve RARB genleri, aynı hastalarda ve metilasyon fenotipinin üyeleri arasında önemli ölçüde
birlikte metillendi.
Sonuç: Çalışmamız, DNMT3A geninin dramatik bir şekilde yukarı
regüle edildiğini ve metilasyon fenotipi ile anlamlı şekilde korele
olduğunu gösterdi.

Keywords

• Metilatör fenotipi
• MSP
• epigenetik
• tümör baskılayıcı genler
• akut miyeloid lösemi
• DNA metiltransferazlar

ER, SOCS1, p15, E-cadherin and RARB are more Likely to be Members of the Methylator Phenotype of Adult and Childhood AML and Their Methylation is Primarly Regulated by an Overexpression of DNMT 3A

Abstract

Objectives: The hypermethylator phenotype is used as a term for
both acute myeloid leukemia (AML) and other tumors. We analyzed the methylation statuses of ten genes (DAP-kinase, SOCS1,
ER, p15, Ecadherin, RARβ, p16, GSTP1, HIC1 and p73) and correlated them with the expression of DNA methyltransferases (DNMTs).
Material and Method: We analyzed the methylation profiles using
methylation specific PCR and COBRA and the expression of DNMTs
(DNMT 1, 3A and 3B) by quantitative RT-PCR in 25 pediatric and 25
adult AML samples.
Results: The ER, SOCS1, p15, E cadherin, and RARB genes methylated together significantly in the same patients and members of
the methylator phenotype.
Conclusion: Our study demonstrated that the gene DNMT3A was
dramatically upregulated and significantly correlated with the
methylator phenotype.

Keywords

• MSP
• Methylator phenotype
• epigenetics
• tumor-suppressor genes
• acute myeloid leukemia
• DNA methyltransferases

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