Epigenetic dysregulation of secreted Frizzled-related proteins in multiple myeloma
Epigenetic dysregulation of secreted Frizzled-related proteins in multiple myeloma
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DOI：
10.1016/j.canlet.2009.02.002
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发表时间：
2009-08-18
期刊：
影响因子：
9.7
通讯作者：
Galm, O.
中科院分区：
文献类型：
--
作者：
Jost, E.;Gezer, D.;Galm, O.
我们分析了 Wnt 通路表观遗传失调对恶性浆细胞疾病的临床影响。在多发性骨髓瘤 (MM) 细胞系中，分泌的卷曲相关蛋白 (SFRP) 基因的异常启动子高甲基化是常见事件，SFRP1、-2 和 -5 的高甲基化与转录沉默相关。在 76 个主要患者样本中，SFRPI 的异常甲基化频率为 35.5%，SFRP2 为 52.6%，SFRP4 为 1.3%，SFRP5 为 6.9%。在意义未明的单克隆丙种球蛋白病和包括浆细胞白血病 (PCL) 在内的所有 MM 阶段中检测到 SFRPI 和 -2 基因的高甲基化，而 SFRP5 甲基化仅限于晚期 MM 阶段和 PCL。我们的数据表明，Wnt 拮抗剂的表观遗传沉默是 MM 发病机制的早期事件，SFRP5 高甲基化可能在疾病进展中发挥作用。 (C) 2009 Elsevier Ireland Ltd. 保留所有权利。
We analysed the clinical impact of epigenetic dysregulation of the Wnt pathway in malignant plasma cell disorders. In multiple myeloma (MM) cell lines, aberrant promoter hypermethylation of the secreted Frizzled-related protein (SFRP) genes was a common event, and hypermethylation of SFRP1, -2 and -5 was associated with transcriptional silencing. Among 76 primary patient samples, the frequency of aberrant methylation was 35.5% for SFRPI, 52.6% for SFRP2, 1.3% for SFRP4 and 6.9% for SFRP5. Hypermethylation of SFRPI and -2 genes was detected in monoclonal gammopathy of undetermined significance and all MM stages including plasma cell leukaemia (PCL), while SFRP5 methylation was restricted to advanced MM stages and PCL. Our data indicate that epigenetic silencing of Wnt antagonists is an early event in MM pathogenesis and that SFRP5 hypermethylation may play a role in disease progression. (C) 2009 Elsevier Ireland Ltd. All rights reserved.