文章：

T细胞淋巴母细胞白血病和淋巴瘤的DNA甲基化与拷贝数变异分析

DNA methylation and copy number variation profiling of T-cell lymphoblastic leukemia and lymphoma

原文发布日期：2020-04-28

DOI: 10.1038/s41408-020-0310-9

类型: Article

开放获取: 是

英文摘要：

Despite having common overlapping immunophenotypic and morphological features, T-cell lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) have distinct clinical manifestations, which may represent separate diseases. We investigated and compared the epigenetic and genetic landscape of adult and pediatric T-ALL (n = 77) and T-LBL (n = 15) patient samples by high-resolution genome-wide DNA methylation and Copy Number Variation (CNV) BeadChip arrays. DNA methylation profiling identified the presence of CpG island methylator phenotype (CIMP) subgroups within both pediatric and adult T-LBL and T-ALL. An epigenetic signature of 128 differentially methylated CpG sites was identified, that clustered T-LBL and T-ALL separately. The most significant differentially methylated gene loci included the SGCE/PEG10 shared promoter region, previously implicated in lymphoid malignancies. CNV analysis confirmed overlapping recurrent aberrations between T-ALL and T-LBL, including 9p21.3 (CDKN2A/CDKN2B) deletions. A significantly higher frequency of chromosome 13q14.2 deletions was identified in T-LBL samples (36% in T-LBL vs. 0% in T-ALL). This deletion, encompassing the RB1, MIR15A and MIR16-1 gene loci, has been reported as a recurrent deletion in B-cell malignancies. Our study reveals epigenetic and genetic markers that can distinguish between T-LBL and T-ALL, and deepen the understanding of the biology underlying the diverse disease localization.
 

摘要翻译： 

尽管T淋巴细胞白血病（T-ALL）与淋巴瘤（T-LBL）具有重叠的免疫表型和形态学特征，但二者临床表现存在显著差异，可能提示二者属于不同疾病。我们通过高分辨率全基因组DNA甲基化和拷贝数变异芯片阵列，对成人及儿童T-ALL（77例）与T-LBL（15例）患者样本的表观遗传和遗传特征进行了比较研究。DNA甲基化分析发现儿童和成人T-LBL及T-ALL中均存在CpG岛甲基化表型亚组。研究鉴定出128个差异甲基化CpG位点的表观遗传特征，可有效区分T-LBL与T-ALL。其中最显著的差异甲基化基因位点包括与淋巴恶性肿瘤相关的SGCE/PEG10共享启动子区域。拷贝数变异分析证实了T-ALL与T-LBL共有的重复性异常，包括9p21.3区域（CDKN2A/CDKN2B）缺失。值得注意的是，T-LBL样本中13q14.2染色体缺失频率显著更高（T-LBL为36% vs T-ALL为0%）。该缺失区域涵盖RB1、MIR15A和MIR16-1基因位点，既往研究报道其为B细胞恶性肿瘤的常见缺失。本研究揭示了能够区分T-LBL与T-ALL的表观遗传和遗传标志物，深化了对疾病定位差异背后生物学机制的理解。

原文链接：

DNA methylation and copy number variation profiling of T-cell lymphoblastic leukemia and lymphoma