Saied Marwa H, Marzec Jacek, Khalid Sabah, Smith Paul, Molloy Gael, Young Bryan D
Centre for Haemato-Oncology, Barts Cancer Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom. ; Clinical Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Centre for Haemato-Oncology, Barts Cancer Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom. ; Centre for Molecular Oncology, Barts Cancer Institute, Barts and the London School of Medicine, Queen Mary University of London, London, United Kingdom.
Biomark Cancer. 2015 Jan 29;7:1-6. doi: 10.4137/BIC.S19614. eCollection 2015.
Trisomy 8 acute myeloid leukemia (AML) is the commonest numerical aberration in AML. Here we present a global analysis of trisomy 8 AML using methylated DNA immunoprecipitation-sequencing (MeDIP-seq). The study is based on three diagnostic trisomy 8 AML and their parallel relapse status in addition to nine non-trisomic AML and four normal bone marrows (NBMs). In contrast to non-trisomic DNA samples, trisomy 8 AML showed a characteristic DNA methylation distribution pattern because an increase in the frequency of the hypermethylation signals in chromosome 8 was associated with an increase in the hypomethylation signals in the rest of the chromosomes. Chromosome 8 hypermethylation signals were found mainly in the CpG island (CGI) shores and interspersed repeats. Validating the most significant differentially methylated CGI (P = 7.88 × 10(-11)) identified in trisomy 8 AML demonstrated a specific core region within the gene body of HHEX, which was significantly correlated with HHEX expression in both diagnostic and relapse trisomy 8 AMLs. Overall, the existence of extra chromosome 8 was associated with a global impact on the DNA methylation distribution with identification of HHEX gene methylation as a potential diagnostic marker for trisomy 8 AML.
8号染色体三体急性髓系白血病（AML）是AML中最常见的数目异常。在此，我们使用甲基化DNA免疫沉淀测序（MeDIP-seq）对8号染色体三体AML进行了全面分析。该研究基于3例诊断为8号染色体三体的AML及其相应的复发状态，另外还有9例非三体AML和4例正常骨髓（NBM）。与非三体DNA样本相比，8号染色体三体AML呈现出特征性的DNA甲基化分布模式，因为8号染色体上高甲基化信号频率的增加与其余染色体上低甲基化信号的增加相关。8号染色体高甲基化信号主要见于CpG岛（CGI）边缘和散在重复序列。对在8号染色体三体AML中鉴定出的最显著差异甲基化CGI（P = 7.88 × 10(-11)）进行验证，结果显示在HHEX基因体内存在一个特定的核心区域，该区域在诊断和复发的8号染色体三体AML中均与HHEX表达显著相关。总体而言，额外的8号染色体的存在对DNA甲基化分布产生了全局性影响，鉴定出HHEX基因甲基化作为8号染色体三体AML的潜在诊断标志物。
