Differential DNA methylation patterns of small B-cell lymphoma subclasses with different clinical behavior
Differential DNA methylation patterns of small B-cell lymphoma subclasses with different clinical behavior
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DOI：
10.1038/sj.leu.2404345
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发表时间：
2006-10-01
期刊：
影响因子：
11.4
通讯作者：
Caldwell, C. W.
中科院分区：
文献类型：
--
作者：
Rahmatpanah, F. B.;Carstens, S.;Caldwell, C. W.
非霍奇金淋巴瘤（non-Hodgkin's lymphoma，NHL）是一组具有多种临床表现和分子特征的免疫系统恶性肿瘤。尽管在基于经典方法的NHL分类方面取得了进展，但分子分类仍在进行中。为了实现这一目标，我们使用了一种称为差异甲基化杂交（DMH）的基于阵列的技术来研究小B细胞淋巴瘤（SBCL）亚型。总共进行了43个基因组DMH实验。根据这些结果，使用几种统计方法来生成一组差异甲基化基因以供进一步验证。在细胞系和患者样本中验证了LHX 2、POU 3F 3、HOXC 10、NRP 2、PRKCE、RAMP、MLLT 2、NKX6.1、LRP 1B和ARF 4的甲基化，并证明了亚型相关的优先甲基化模式。对于LHX 2和LRP 1B，亚硫酸氢盐测序、实时逆转录酶-聚合酶链反应和用去甲基化剂5 '-氮杂-2'-脱氧胞苷处理后的基因表达诱导得到证实。这种新的表观遗传学信息有助于定义目前分类系统未识别的SBCL不同亚型的分子特征，并为这些肿瘤的生物学提供有价值的潜在见解。
Non-Hodgkin's lymphoma ( NHL) is a group of malignancies of the immune system with variable clinical behaviors and diverse molecular features. Despite the progress made in classification of NHLs based on classical methods, molecular classifications are a work in progress. Toward this goal, we used an array-based technique called differential methylation hybridization ( DMH) to study small B-cell lymphoma ( SBCL) subtypes. A total of 43 genomic DMH experiments were performed. From these results, several statistical methods were used to generate a set of differentially methylated genes for further validation. Methylation of LHX2, POU3F3, HOXC10, NRP2, PRKCE, RAMP, MLLT2, NKX6.1, LRP1B and ARF4 was validated in cell lines and patient samples and demonstrated subtype-related preferential methylation patterns. For LHX2 and LRP1B, bisulfite sequencing, real-time reverse transcriptase-polymerase chain reaction and induction of gene expression following treatment with the demethylating agent, 5'-aza-2'-deoxycytidine, were confirmed. This new epigenetic information is helping to define molecular portraits of distinct subtypes of SBCL that are not recognized by current classification systems and provides valuable potential insights into the biology of these tumors.