Epigenetic analysis of childhood acute lymphoblastic leukemia
Epigenetic analysis of childhood acute lymphoblastic leukemia
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DOI：
10.4161/epi.4.3.8752
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发表时间：
2009-04-01
期刊：
影响因子：
3.7
通讯作者：
Latif, Farida
中科院分区：
文献类型：
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作者：
Dunwell, Thomas L.;Hesson, Luke B.;Latif, Farida
我们使用3号染色体NotI基因芯片鉴定儿童急性淋巴细胞白血病（ALL）表观遗传学失活基因。三个新基因在儿童ALL中表现出频繁的甲基化。PPP 2 R3 A（蛋白磷酸酶2，调节亚基B“，a）在T（69%）和B（82%）-ALL中频繁甲基化。虽然FBLN 2（fibulin 2）和THRB（甲状腺激素受体，β）在B-ALL中频繁甲基化（分别为58%; 56%），但在T-ALL中甲基化频率较低（两种基因均为17%）。最近，研究表明，BNC 1（Basonuclin 1）和MSX 1（msh homeobox 1）在常见的上皮癌中经常甲基化。在我们的儿童ALL系列中，BNC 1在T（77%）和B-ALL（79%）中经常甲基化，而MSX 1显示T-ALL（25%）特异性甲基化。上述5个基因的甲基化是肿瘤特异性的，在5-氮杂-2 '-脱氧胞苷处理的甲基化白血病细胞系中，这些基因的表达可以恢复。这是第一份证明PPP 2 R3 A、FBLN 2、THRB、BNC 1和MSX 1在白血病中频繁表观遗传失活的报告。鉴定显示癌症特异性甲基化的频繁甲基化基因将有助于开发早期癌症检测筛查和靶向表观遗传治疗。
We used a chromosome 3 wide NotI microarray for identification of epigenetically inactivated genes in childhood acute lymphoblastic leukemia (ALL). Three novel genes demonstrated frequent methylation in childhood ALL. PPP2R3A (protein phosphatase 2, regulatory subunit B'', a) was frequently methylated in T (69%) and B (82%)-ALL. Whilst FBLN2 (fibulin 2) and THRB (thyroid hormone receptor, beta) showed frequent methylation in B-ALL (58%; 56% respectively), but were less frequently methylated in T-ALL (17% for both genes). Recently it was demonstrated that BNC1 (Basonuclin 1) and MSX1 (msh homeobox 1) were frequently methylated across common epithelial cancers. In our series of childhood ALL BNC1 was frequently methylated in both T (77%) and B-ALL (79%), whilst MSX1 showed T-ALL (25%) specific methylation. The methylation of the above five genes was cancer specific and expression of the genes could be restored in methylated leukemia cell lines treated with 5-aza-2'-deoxycytidine. This is the first report demonstrating frequent epigenetic inactivation of PPP2R3A, FBLN2, THRB, BNC1 and MSX1 in leukemia. The identification of frequently methylated genes showing cancer specific methylation will be useful in developing early cancer detection screens and for targeted epigenetic therapies.