Abstract Objective To investigate the methylation status of zonula occludens-1 (ZO-1) gene promoter and its clinical significance in children with stage IV non-Hodgkin lymphoma (NHL) and to provide a basis for further etiological study and early diagnosis of this disease. Methods Fifty-five children with a confirmed diagnosis of stage IV NHL (40 cases of T-NHL and 15 cases of B-NHL) were selected as the case group, and 20 children with diseases other than hematologic malignancies were selected as the control group. Bone marrow samples were collected from these subjects. Methylation-specific PCR (MS-PCR) was applied to evaluate the methylation status of ZO-1 gene promoter, and the integrated optical density (IOD) was determined. RT-PCR was used to measure the mRNA expression of ZO-1. Results MS-PCR showed that the methylated bands of ZO-1 gene promoter were found in 39 (70.9%) of 55 patients in the case group before treatment, while no ZO-1 gene promoter methylation was detected in the control group. With close tracking of 47 cases in the study group, consisting of 32 cases of T-NHL and 15 cases of B-NHL, the rates of ZO-1 gene promoter methylation prior to treatment were 72% and 67%, respectively, (P>0.572). The cases of T-NHL and B-NHL showed no significant changes in methylation rate in the early and middle phases of chemotherapy (P>0.05), but they showed significant changes in methylation rate in the late phase of chemotherapy (Pr=0.093, P=0.575); a positive correlation was found between the number of malignant cells in bone marrow and ZO-1 gene IOD (r=0.669, PConclusions ZO-1 gene shows a hypermethylation status in children with NHL, and the methylation level is positively correlated with the number of malignant cells in bone marrow. ZO-1 may be used as a novel molecular marker in early diagnosis, outcome assessment, prognostic evaluation, and detection of minimal residual disease.
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Cite this article:
DIAO Yu-Qiao,QU Fan,YANG Ming-Juan et al. ZO-1 gene methylation status and its clinical significance in children with non- Hodgkin lymphoma[J]. CJCP, 2014, 16(6): 619-623.
DIAO Yu-Qiao,QU Fan,YANG Ming-Juan et al. ZO-1 gene methylation status and its clinical significance in children with non- Hodgkin lymphoma[J]. CJCP, 2014, 16(6): 619-623.
Jeltsch A. Beyond Watson and Crick: DNA methylation and molecular enzymology of DNA methyltransferases[J].Chembiochem, 2002, 3(5): 274-293.
3.0.CO;2-S target="_blank">
[7]
Cheng X, Roberts RJ. AdoMet-dependent methylation, DNA methylt-ransferases and base flipping[J].Nucleic Acids Res, 2001, 29(18): 3784-3795.
Costello JF, Plass C. Methylation matters[J].J Med Genet, 2001, 38(5): 285-303.
[10]
Fanning AS, Ma TY, Anderson JM. Isolation and functional characterization of the actin binding region in the tight junction protein ZO-1[J].FASEB J, 2002, 16(13): 1835.
