Jost E, Gezer D, Wilop S, Suzuki H, Herman J G, Osieka R, Galm O
Medizinische Klinik IV, Universitaetsklinikum Aachen, RWTH Aachen, Germany.
Cancer Lett. 2009 Aug 18;281(1):24-31. doi: 10.1016/j.canlet.2009.02.002. Epub 2009 Mar 18.
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 SFRP1, 52.6% for SFRP2, 1.3% for SFRP4 and 6.9% for SFRP5. Hypermethylation of SFRP1 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.
我们分析了Wnt信号通路表观遗传失调在恶性浆细胞疾病中的临床影响。在多发性骨髓瘤（MM）细胞系中，分泌型卷曲相关蛋白（SFRP）基因启动子异常高甲基化是常见现象，SFRP1、-2和-5的高甲基化与转录沉默相关。在76例原发性患者样本中，SFRP1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以及包括浆细胞白血病（PCL）在内的所有MM阶段中均检测到SFRP1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发病机制中的早期事件，且SFRP5高甲基化可能在疾病进展中起作用。
