Identification of aberrant methylation regions in neuroblastoma by screening of tissue-specific differentially methylated regions.
Identification of aberrant methylation regions in neuroblastoma by screening of tissue-specific differentially methylated regions.
复制标题
通过筛选组织特异性差异甲基化区域来鉴定神经母细胞瘤中的异常甲基化区域。
DOI：
10.1002/pbc.24282
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发表时间：
2013
影响因子：
3.2
通讯作者：
Ghosh,Srimoy
中科院分区：
文献类型：
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作者：
Sugito,Kiminobu;Kawashima,Hiroyuki;Uekusa,Shota;Yoshizawa,Shinsuke;Hoshi,Reina;Furuya,Takeshi;Kaneda,Hide;Hosoda,Toshifumi;Masuko,Takayuki;Ohashi,Kensuke;Ikeda,Taro;Koshinaga,Tsugumichi;Fujiwara,Kyoko;Igarashi,Jun;Ghosh,Srimoy
组织特异性差异甲基化区域(TDMRS)的识别是我们理解哺乳动物发育的关键。研究表明，tDMRS在癌症中异常甲基化，并可能影响肿瘤的形成过程。我们使用Massarray EpiTYPER系统测定了7例神经母细胞瘤(NBS)和2例对照肾上腺髓质在12个保守的tDMR上的甲基化水平。第二个样本集的19个国家统计局也进行了分析。结果对12个tDMR进行筛选，发现2个基因组区域(SLC16A5和ZNF206)在鼻咽癌中存在频繁的异常甲基化模式。与对照肾上腺髓质相比，SLC16A5和ZNF206的甲基化水平较低。SLC16A5基因甲基化水平(切断点13.25%)与确诊年龄、疾病分期、Shimada分级有关，但与MYCN扩增无关。ZNF206基因甲基化水平(截断点，68.80%)与所有预后因素相关。虽然在单变量分析中，这些区域的甲基化水平与预后的相关性没有达到统计学意义，但同时存在SLC16A5低甲基化和ZNF206高甲基化的患者，当这两个变量一起分析时，患者的无事件生存期显著延长。结论我们发现两个tDMR经常在NB基因组中表现出甲基化模式的改变，提示它们参与了NB的发生/分化。这两个区域的联合分析可以作为临床结果较差的诊断生物标记物。儿科血癌2013；60：383-389。©2012 Wiley期刊，Inc.
BackgroundThe identification of tissue‐specific differentially methylated regions (tDMRs) is key to our understanding of mammalian development. Research has indicated that tDMRs are aberrantly methylated in cancer and may affect the oncogenic process.ProcedureWe used the MassARRAY EpiTYPER system to determine the quantitative methylation levels of seven neuroblastomas (NBs) and two control adrenal medullas at 12 conserved tDMRs. A second sample set of 19 NBs was also analyzed. Statistical analysis was carried out to determine the relationship of the quantitative methylation levels to other prognostic factors in these sample sets.ResultsScreening of 12 tDMRs revealed 2 genomic regions (SLC16A5andZNF206) with frequent aberrant methylation patterns in NB. The methylation levels ofSLC16A5andZNF206were low compared to the control adrenal medullas. TheSLC16A5methylation level (cut‐off point, 13.25%) was associated with age at diagnosis, disease stage, and Shimada classification but not withMYCNamplification. TheZNF206methylation level (cut‐off point, 68.80%) was associated with all of the prognostic factors analyzed. Although the methylation levels at these regions did not reach statistical significance in their association with prognosis in mono‐variant analysis, patients with both hypomethylation ofSLC16A5and hypermethylation ofZNF206had a significantly prolonged event‐free survival, when these two variables were analyzed together.ConclusionsWe demonstrated that two tDMRs frequently displayed altered methylation patterns in the NB genome, suggesting their distinct involvement in NB development/differentiation. The combined analysis of these two regions could serve as a diagnostic biomarker for poor clinical outcome. Pediatr Blood Cancer 2013; 60: 383–389. © 2012 Wiley Periodicals, Inc.