Scholz Christian, Nimmrich Inko, Burger Matthias, Becker Evelyne, Dörken Bernd, Ludwig Wolf-Dieter, Maier Sabine
Department of Hematology and Oncology, Universitätsmedizin Berlin, Charité Campus Virchow-Klinikum, Berlin, Germany.
Ann Hematol. 2005 Apr;84(4):236-44. doi: 10.1007/s00277-004-0969-1. Epub 2004 Nov 6.
Patterns of DNA methylation are substantially altered in malignancies compared to normal tissue, with both genome-wide hypomethylation and regional increase of cytosine methylation at dinucleotides of cytosine and guanine, i.e., CpG dinucleotides. While genome-wide hypomethylation renders chromosomes instable, hypermethylation of CpGs in promoter regions is generally associated with transcriptional silencing, e.g., of tumor suppressor genes. To investigate whether disease-specific methylation profiles exist for different entities of acute leukemia, a microarray-based DNA methylation analysis simultaneously assessing 249 CpG dinucleotides originating from 57 genes was employed. Hereby, samples from precursor B-cell acute lymphoblastic leukemia (ALL) could be distinguished from cases of acute myeloid leukemia by virtue of N33, EGR4, CDC2, CCND2, or MOS hypermethylation in ALL.
与正常组织相比，恶性肿瘤中的DNA甲基化模式发生了显著改变，出现了全基因组低甲基化以及胞嘧啶和鸟嘌呤二核苷酸（即CpG二核苷酸）区域的胞嘧啶甲基化增加。全基因组低甲基化会使染色体不稳定，而启动子区域CpG的高甲基化通常与转录沉默相关，例如肿瘤抑制基因的转录沉默。为了研究不同类型的急性白血病是否存在疾病特异性的甲基化谱，我们采用了基于微阵列的DNA甲基化分析，同时评估来自57个基因的249个CpG二核苷酸。据此，前体B细胞急性淋巴细胞白血病（ALL）样本可通过ALL中N33、EGR4、CDC2、CCND2或MOS的高甲基化与急性髓系白血病病例区分开来。
