Novel methylation targets in de novo acute myeloid leukemia with prevalence of chromosome 11 loci.
Novel methylation targets in de novo acute myeloid leukemia with prevalence of chromosome 11 loci.
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DOI：
10.1182/blood.v97.10.3226
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发表时间：
2001-05
期刊：
影响因子：
20.3
通讯作者：
L. Rush;Zunyan Dai;D. Smiraglia;Xin Gao;Fred A. Wright;M. Frühwald;Joseph F. Costello;William A. Held;Li Yu;Ralf Krahe;J. Kolitz;Clara D. Bloomfield;M. Caligiuri;Christoph Plass
中科院分区：
文献类型：
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作者：
L. Rush;Zunyan Dai;D. Smiraglia;Xin Gao;Fred A. Wright;M. Frühwald;Joseph F. Costello;William A. Held;Li Yu;Ralf Krahe;J. Kolitz;Clara D. Bloomfield;M. Caligiuri;Christoph Plass
异常的DNA甲基化被认为在肿瘤发生中是重要的，通过引起基因的转录失活或染色体不稳定。几个实验室已经确定了急性髓细胞白血病（AML）中肿瘤抑制基因的启动子超甲基化。然而，这些研究没有提供总体甲基化变化的总体评估，也不能识别新的甲基化序列。以前，非随机CpG岛甲基化的报道，在17个成人初发AML诊断样本相比，相应的缓解样本通过限制性标志基因组扫描（RLGS）。该研究通过分析更大的CpG岛（1740 vs 1184）进行了扩展，现在提供了33个克隆甲基化位点的详细信息，包括21个已知基因或表达的序列标签。这些克隆的基因座中有5个似乎仅在AML中甲基化，而在本研究中研究的6种实体瘤中没有甲基化（分析了超过98个样品）。33个基因座中有30个基因座的染色体位置可用，这30个基因座中有5个（17%）定位于11号染色体，表明该染色体上甲基化事件的过度表达趋势。这些结果为AML中广泛的异常甲基化提供了证据，鉴定了新的甲基化靶点，AML特有的表观遗传学变化以及11号染色体上明显的优先甲基化。
Aberrant DNA methylation is believed to be important in tumorigenesis by causing either transcriptional inactivation of genes or chromosomal instability. Several laboratories have identified promoter hypermethylation of tumor suppressor genes in acute myeloid leukemia (AML). However, these studies do not provide a global assessment of overall methylation changes and do not allow the identification of novel methylated sequences. Previously, nonrandom CpG island methylation was reported in 17 adult de novo AML diagnostic samples when compared with the corresponding remission samples by means of restriction landmark genomic scanning (RLGS). That study has been expanded on by an analysis of a larger set of CpG islands (1740 vs 1184), which now provides details of 33 cloned methylated loci, including 21 known genes or expressed sequence tags. Five of these cloned loci appear to be methylated only in AML and not in the 6 solid tumors studied in this study (more than 98 samples analyzed). Chromosomal location was available for 30 of the 33 loci, and 5 of these 30 (17%) are localized to chromosome 11, suggesting a trend toward overrepresentation of methylation events on this chromosome. These results provide evidence for widespread aberrant methylation in AML, with identification of novel methylation targets, epigenetic changes that appear unique to AML, and apparent preferential methylation on chromosome 11.