复发性儿童急性淋巴细胞白血病中多个基因启动子相关CpG岛的异常甲基化。

Aberrant methylation in promoter-associated CpG islands of multiple genes in relapsed childhood acute lymphoblastic leukemia.

作者信息

Matsushita Chise, Yang Yang, Takeuchi Seisho, Matsushita Masahide, Van Dongen Jacques J M, Szczepanski Tomasz, Bartram Claus R, Seo Hiromi, Koeffler H Phillip, Taguchi Hirokuni

机构信息

Department of Medicine, Kochi Medical School, Kochi 783-8505, Japan.

出版信息

Oncol Rep. 2004 Jul;12(1):97-9.

PMID:15201966

Abstract

Methylation profile was analyzed in nine cases of relapsed childhood acute lymphoblastic leukemia (ALL) for p14, p15, p16, Rb, MGMT, APC, hMLH1, RARbeta, RIZ, DAPK, and FHIT genes by using methylation specific polymerase chain reaction (MSP) analysis. Frequency of methylation in each gene was: MGMT, 56%; RARbeta, 44%; and p16, 22%, respectively. None of the p14, p15, Rb, APC, hMLH1, RIZ, DAPK, and FHIT genes were hypermethylated. Five (56%) of 9 cases showed methylation of at least one gene. All of the samples with hypermethylation in p16 and MGMT gene at relapse, had already acquired the change at the time of initial diagnosis. Interestingly, three of 4 cases with RARbeta gene methylation at relapse did not have methylation of this gene at the time of initial presentation. These results suggest that hypermethylation might be involved in the relapse of childhood ALL.

摘要

通过甲基化特异性聚合酶链反应（MSP）分析，对9例复发性儿童急性淋巴细胞白血病（ALL）患者的p14、p15、p16、Rb、MGMT、APC、hMLH1、RARβ、RIZ、DAPK和FHIT基因的甲基化谱进行了分析。每个基因的甲基化频率分别为：MGMT，56%；RARβ，44%；p16，22%。p14、p15、Rb、APC、hMLH1、RIZ、DAPK和FHIT基因均未发生高甲基化。9例中有5例（56%）至少有一个基因发生甲基化。所有在复发时p16和MGMT基因发生高甲基化的样本，在初始诊断时就已出现这种变化。有趣的是，4例在复发时RARβ基因发生甲基化的患者中，有3例在初次就诊时该基因并未发生甲基化。这些结果表明，高甲基化可能与儿童ALL的复发有关。