Concurrent methylation of multiple genes in childhood ALL: Correlation with phenotype and molecular subgroup
Concurrent methylation of multiple genes in childhood ALL: Correlation with phenotype and molecular subgroup
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DOI：
10.1038/sj.leu.2403060
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发表时间：
2003-09-01
期刊：
影响因子：
11.4
通讯作者：
Bhatia, K
中科院分区：
文献类型：
--
作者：
Gutierrez, MI;Siraj, AK;Bhatia, K
多个基因已被证明是独立的高甲基化淋巴恶性肿瘤。我们在此报告了129例儿童ALL中E-钙粘蛋白、Dap-激酶、O（6）MGMT、p73、p16、p15和p14同时甲基化的程度。虽然这些基因中的大多数在一定比例的病例中表现出甲基化，但O-6 MGMT、p16和p14很少甲基化（分别为11%、7%和3%）。在绝大多数（83%）病例中发现至少一个基因的甲基化。为了确定甲基化的程度和一致性，我们计算了每个样品的甲基化指数（MI =甲基化基因的数量/研究基因的数量）。平均MI为0.28，对应于2/7的甲基化基因。MI与标准预后因素相关，包括免疫表型、年龄、性别、WBC和存在特异性易位（TEL-AML 1、BCR-ABL、E2 A-PBX 1或MLL-AF 4）。我们确定大于或等于10岁的儿童和白细胞增高（大于或等于50 × 10（9）/l）的儿童均与较高的MI相关（P
Multiple genes have been shown to be independently hypermethylated in lymphoid malignancies. We report here on the extent of concurrent methylation of E-cadherin, Dap-kinase, O(6)MGMT, p73, p16, p15 and p14 in 129 pediatric ALL cases. While most of these genes demonstrated methylation in a proportion of cases, O-6 MGMT, p16 and p14 were infrequently methylated (11, 7 and 3%, respectively). Methylation of at least one gene was found in the vast majority (83%) of cases. To determine the extent and concordance of methylation we calculated a methylation index (MI = number of methylated genes/number of studied genes) for each sample. The average MI was 0.28, corresponding to 2/7 methylated genes. MI was correlated with standard prognostic factors, including immunophenotype, age, sex, WBC and presence of specific translocations (TEL-AML1, BCR-ABL, E2A-PBX1 or MLL-AF4). We determined that children greater than or equal to10 years old and children presenting with high WBC (greater than or equal to50 x 10(9)/l) both associated with a higher MI (P