Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma.
Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma.
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DOI：
10.1186/1471-2407-13-608
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发表时间：
2013-12-27
期刊：
影响因子：
3.8
通讯作者：
Joh K
中科院分区：
文献类型：
--
作者：
Rumbajan JM;Maeda T;Souzaki R;Mitsui K;Higashimoto K;Nakabayashi K;Yatsuki H;Nishioka K;Harada R;Aoki S;Kohashi K;Oda Y;Hata K;Saji T;Taguchi T;Tajiri T;Soejima H;Joh K
在人类11p15.5的印记差异甲基化区域（DMR）的异常甲基化已在包括肝母细胞瘤在内的许多肿瘤中报道。然而，分散在人类基因组中的印迹基因座中的印迹DMR的甲基化状态尚未在任何肿瘤中进行分析。采用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）结合焦磷酸测序技术，分析了12例肝母细胞瘤及癌旁正常肝组织中33个印迹DMR的甲基化状态。用DNA多态性研究单亲二体性（UPD）和拷贝数异常。在分析的33个DMR中，18个在至少1个肿瘤中显示异常甲基化。DMR中异常甲基化的发生率存在较大的差异。KvDMR 1和IGF 2-DMR 0是最常见的低甲基化DMR。INPP 5 Fv 2-DMR和RB 1-DMR高甲基化频率较高。不仅在肿瘤中，而且在少量相邻的组织学正常的肝组织中，在某些DMR处观察到低甲基化，而仅在肿瘤样品中观察到高甲基化。肿瘤组织和正常肝脏对照组的长散布核元件-1（LINE-1）的甲基化水平没有显示出很大的差异。在某些肿瘤中也发现了染色体异常。11p15.5和20q13.3基因座显示了遗传和表观遗传改变的频繁发生。我们的分析显示，在12例肝母细胞瘤的一些印记DMR中存在肿瘤特异性异常高甲基化，并进一步提示了肿瘤发生前低甲基化的可能性。有些位点同时表现出遗传和表观遗传的高频率变异。这些发现将有助于了解肝母细胞瘤的发展。
Aberrant methylation at imprinted differentially methylated regions (DMRs) in human 11p15.5 has been reported in many tumors including hepatoblastoma. However, the methylation status of imprinted DMRs in imprinted loci scattered through the human genome has not been analyzed yet in any tumors. The methylation statuses of 33 imprinted DMRs were analyzed in 12 hepatoblastomas and adjacent normal liver tissue by MALDI-TOF MS and pyrosequencing. Uniparental disomy (UPD) and copy number abnormalities were investigated with DNA polymorphisms. Among 33 DMRs analyzed, 18 showed aberrant methylation in at least 1 tumor. There was large deviation in the incidence of aberrant methylation among the DMRs. KvDMR1 and IGF2-DMR0 were the most frequently hypomethylated DMRs. INPP5Fv2-DMR and RB1-DMR were hypermethylated with high frequencies. Hypomethylation was observed at certain DMRs not only in tumors but also in a small number of adjacent histologically normal liver tissue, whereas hypermethylation was observed only in tumor samples. The methylation levels of long interspersed nuclear element-1 (LINE-1) did not show large differences between tumor tissue and normal liver controls. Chromosomal abnormalities were also found in some tumors. 11p15.5 and 20q13.3 loci showed the frequent occurrence of both genetic and epigenetic alterations. Our analyses revealed tumor-specific aberrant hypermethylation at some imprinted DMRs in 12 hepatoblastomas with additional suggestion for the possibility of hypomethylation prior to tumor development. Some loci showed both genetic and epigenetic alterations with high frequencies. These findings will aid in understanding the development of hepatoblastoma.
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影响因子：
14.9
作者：
Monk D;Arnaud P;Frost JM;Wood AJ;Cowley M;Martin-Trujillo A;Guillaumet-Adkins A;Iglesias Platas I;Camprubi C;Bourc'his D;Feil R;Moore GE;Oakey RJ
通讯作者：
Oakey RJ
影响因子：
4
作者：
Hancks, Dustin C.;Kazazian, Haig H., Jr.
通讯作者：
Kazazian, Haig H., Jr.
影响因子：
2
作者：
Higashimoto, Ken;Nakabayashi, Kazuhiko;Soejima, Hidenobu
通讯作者：
Soejima, Hidenobu
影响因子：
50.3
作者：
Holm, TM;Jackson-Grusby, L;Jaenisch, R
通讯作者：
Jaenisch, R
影响因子：
30.8
作者：
MOULTON, T;CRENSHAW, T;TYCKO, B
通讯作者：
TYCKO, B