TGFβR2 aberrant methylation is a potential prognostic marker and therapeutic target in multiple myeloma
TGFβR2 aberrant methylation is a potential prognostic marker and therapeutic target in multiple myeloma
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DOI：
10.1002/ijc.24431
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发表时间：
2009-10-15
影响因子：
6.4
通讯作者：
Vettore, Andre L.
中科院分区：
文献类型：
--
作者：
de Carvalho, Fabricio;Colleoni, Gisele W. B.;Vettore, Andre L.
多发性骨髓瘤（MM）是一种无法治愈的血液恶性肿瘤。不同的研究证明了 MM 中发生了遗传和表观遗传改变。异常甲基化是人类基因组中最常见的表观遗传改变之一。本研究通过定量甲基化特异性PCR（QMSP）评估了51个MM样本中20个基因的异常甲基化状态，并将甲基化谱与患者的临床病理特征进行了比较。 QMSP 分析显示，PTGS2 (100.0%)、SFN (100.0%)、CDKN2B (90.2%)、CDH1 (88.2%)、ESR1 (72.5%)、HIC1 (70.5%)、CCND2 (62.7%)、DCC (45.1%) 和 TGF beta R2 (39.2%) 在MM 而 RAR beta (16.6%)、MGMT (12.5%)、AIM1 (12.5%)、CDKN2A (8.3%)、SOCS1 (8.3%)、CCNA1 (8.3%) 和 THBS1 (4.1%) 的异常甲基化是罕见事件。测试的样品中 GSTP1、MINT31、p14ARF 和 RB1 没有甲基化。 ESR1的高甲基化与IgA同种型呈正相关，而THBS1的异常甲基化与IgG同种型呈负相关。此外，DCC 和 TGF beta R2 的高甲基化与较差的生存率相关。多变量分析显示 ISS 和 TGF beta R2 高甲基化与不良预后密切相关。这项研究代表了对 MM 启动子甲基化的首次定量评估，我们的数据提供了证据，表明除了 ISS 之外，TGF beta R2 高甲基化可能可用作该疾病的预后指标。 (C)2009年UICC
Multiple myeloma (MM) is an incurable hematological malignancy. Different studies demonstrated the occurrence of genetic and epigenetic alterations in MM. The aberrant methylation is one of the most frequent epigenetic alterations in human genome. This study evaluated the aberrant methylation status or 20 genes in 51 MM samples by quantitative methylation-specific PCR (QMSP) and compared the methylation profile with clinicopathological characteristics of the patients. The QMSP analyses showed that PTGS2 (100.0%), SFN (100.0%), CDKN2B (90.2%), CDH1 (88.2%), ESR1 (72.5%), HIC1 (70.5%), CCND2 (62.7%), DCC (45.1%) and TGF beta R2 (39.2%) are frequently hypermethylated in MM while aberrant methviation of RAR beta (16.6%), MGMT (12.5%), AIM1 (12.5%), CDKN2A (8.3%), SOCS1 (8.3%), CCNA1 (8.3%) and THBS1 (4.1%) are rare events. There was no methylation of GSTP1, MINT31, p14ARF and RB1 in the samples tested. Hypermethylation of ESR1 was correlated positively with isotype IgA, while aberrant methylation of THBS1 correlated negatively with isotype IgG. Furthermore, hypermethylation of DCC and TGF beta R2 were correlated with poor survival. The multivariate analysis showed ISS and TGF beta R2 hypermethylation strongly correlated with poor outcome. This study represents the first quantitative evaluation of promoter methylation in MM and our data provide evidence that TGF beta R2 hypermethylation, besides ISS, may be useful as prognostic indicator in this disease. (C) 2009 UICC