DNA methylation profiling reveals common signatures of tumorigenesis and defines epigenetic prognostic subtypes of canine Diffuse Large B-cell Lymphoma.
DNA methylation profiling reveals common signatures of tumorigenesis and defines epigenetic prognostic subtypes of canine Diffuse Large B-cell Lymphoma.
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DOI：
10.1038/s41598-017-11724-w
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发表时间：
2017-09-14
影响因子：
4.6
通讯作者：
Aresu L
中科院分区：
文献类型：
--
作者：
Ferraresso S;Aricò A;Sanavia T;Da Ros S;Milan M;Cascione L;Comazzi S;Martini V;Giantin M;Di Camillo B;Mazzariol S;Giannuzzi D;Marconato L;Aresu L
表观遗传失调是癌症的一个标志，其特征是在CpG岛频繁获得新的DNA甲基化。为了深入了解犬DLBCL的甲基化变化，我们利用全基因组CpG芯片研究了原发DLBCL与对照淋巴结的DNA甲基化变化。与对照相比，我们鉴定出1194个靶位点在肿瘤中显示出不同的甲基化水平。高甲基化的CpG位点包括启动子、5 ' - utr、上游和外显子区域。有趣的是，干细胞中多梳抑制复合体的靶点大多受到影响，这表明DLBCL具有干细胞样表观遗传模式。功能分析强调了与胚胎发育、组织形态发生和细胞分化密切相关的生物学过程，包括HOX、BMP和WNT。此外，表观遗传模式和全基因组甲基化变异性分析确定了cDLBCL亚群。其中一些表观遗传亚型与临床结果一致，支持异常表观遗传变化的积累导致肿瘤更具侵袭性行为的假设。总的来说，我们的研究结果表明DNA甲基化在DLBCL中起重要作用，其中转录因子的异常经常被观察到，表明在肿瘤发生过程中参与。这些发现值得进一步研究，以改善cDLBCL的预后分类，并为肿瘤侵袭性提供新的见解。
Epigenetic deregulation is a hallmark of cancer characterized by frequent acquisition of new DNA methylation in CpG islands. To gain insight into the methylation changes of canine DLBCL, we investigated the DNA methylome in primary DLBCLs in comparison with control lymph nodes by genome-wide CpG microarray. We identified 1,194 target loci showing different methylation levels in tumors compared with controls. The hypermethylated CpG loci included promoter, 5′-UTRs, upstream and exonic regions. Interestingly, targets of polycomb repressive complex in stem cells were mostly affected suggesting that DLBCL shares a stem cell-like epigenetic pattern. Functional analysis highlighted biological processes strongly related to embryonic development, tissue morphogenesis and cellular differentiation, including HOX, BMP and WNT. In addition, the analysis of epigenetic patterns and genome-wide methylation variability identified cDLBCL subgroups. Some of these epigenetic subtypes showed a concordance with the clinical outcome supporting the hypothesis that the accumulation of aberrant epigenetic changes results in a more aggressive behavior of the tumor. Collectively, our results suggest an important role of DNA methylation in DLBCL where aberrancies in transcription factors were frequently observed, suggesting an involvement during tumorigenesis. These findings warrant further investigation to improve cDLBCL prognostic classification and provide new insights on tumor aggressiveness.
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影响因子：
16.6
作者：
Pan, Heng;Jiang, Yanwen;Boi, Michela;Tabbo, Fabrizio;Redmond, David;Nie, Kui;Ladetto, Marco;Chiappella, Annalisa;Cerchietti, Leandro;Shaknovich, Rita;Melnick, Ari M.;Inghirami, Giorgio G.;Tam, Wayne;Elemento, Olivier
通讯作者：
Elemento, Olivier
影响因子：
3.7
作者：
Aricò A;Ferraresso S;Bresolin S;Marconato L;Comazzi S;Te Kronnie G;Aresu L
通讯作者：
Aresu L
影响因子：
2.7
作者：
Bisson, Joseph A.;Mills, Bradley;Cohen, Ethan David
通讯作者：
Cohen, Ethan David
体细胞突变改变生发中心起源的滤泡性和弥漫性大 B 细胞淋巴瘤中的 EZH2 (Tyr641)。
影响因子：
30.8
作者：
Morin, Ryan D.;Johnson, Nathalie A.;Severson, Tesa M.;Mungall, Andrew J.;An, Jianghong;Goya, Rodrigo;Paul, Jessica E.;Boyle, Merrill;Woolcock, Bruce W.;Kuchenbauer, Florian;Yap, Damian;Humphries, R. Keith;Griffith, Obi L.;Shah, Sohrab;Zhu, Henry;Kimbara, Michelle;Shashkin, Pavel;Charlot, Jean F.;Tcherpakov, Marianna;Corbett, Richard;Tam, Angela;Varhol, Richard;Smailus, Duane;Moksa, Michelle;Zhao, Yongjun;Delaney, Allen;Qian, Hong;Birol, Inanc;Schein, Jacqueline;Moore, Richard;Holt, Robert;Horsman, Doug E.;Connors, Joseph M.;Jones, Steven;Aparicio, Samuel;Hirst, Martin;Gascoyne, Randy D.;Marra, Marco A.
通讯作者：
Marra, Marco A.
影响因子：
5.8
作者：
Le, Sebastien;Josse, Julie;Husson, Francois
通讯作者：
Husson, Francois