HIPERMETILASI PROMOTER GEN DKK3, CDH1, DAN APAF1 PADA PASIEN LEUKEMIA LIMFOBLASTIK AKUT ANAK

DNA hypermethylation plays an important role in the inactivation of cancer related genes in hematological neoplasms. Tumor suppressor genes, such as Dickkopfs3 (DKK3), E-Chaderin (CDH1) and Apoptotic protease-activating factor1 (APAF1) were methylated at relatively high frequencies in chilhood acute lymphoblastic leukemia (ALL). Hypermethylation of DKK3, CDH1 and APAF1 implicated in growth-deregulating events, metastasis and impaired apoptosis. The purpose of this study is to investigate the hypermethylation profile of DKK3, CDH1, APAF1 genes and their correlation with age, leukocyte count and immunophenotype in childhood ALL at DR. Sardjito hospital, Yogyakarta. Genomic DNA from pheripheral blood mononuklaers were obtained from 32 chilhood ALL at the time of diagnosis between October 2004 and May 2009. Hypermethylation were detected using the methylation specific polymerase chain reaction (MSP). Statistical analysis was performed using the Fisher's exact test. DKK3, CDH1 and APAF1 were methylated in 18 (56.3%),19 (59.4%) and 26 (81.3%) childhood ALL respectively. Clinical characteristics including age, leukocyte count and immunophenotype did not show significant correlation with hypermethylation status of DKK3, CDH1, APAF1 except for immunophenotype and DKK3 hypermethylation (p = 0.028)