Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns.
Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns.
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DOI：
10.1186/bcr2590
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Ringnér M
中科院分区：
文献类型：
--
作者：
Holm K;Hegardt C;Staaf J;Vallon-Christersson J;Jönsson G;Olsson H;Borg A;Ringnér M
通过基因表达谱分析，已经确定了五种不同的乳腺癌分子亚型。每个亚型都有一个特征性的表达模式，这表明部分取决于细胞来源。我们的目的是调查是否分子亚型也显示不同的甲基化谱。我们使用基于阵列的甲基化检测分析了189个新鲜冷冻的原发性乳腺肿瘤和4个正常乳腺组织样本中807个癌症相关基因的甲基化状态。非监督分析揭示了三组具有特征性甲基化模式的乳腺癌。这三组分别与乳腺癌的管腔A、管腔B和基底样分子亚型相关，而HER2富集和正常样亚型的癌症分布在这三组中。亚型之间的甲基化频率有显著差异，管腔型B和基底细胞样肿瘤甲基化频率分别最高和最低。此外，乳腺癌和胚胎干细胞中的多梳阻遏物复合物的靶点在管腔B肿瘤中比在其他肿瘤中甲基化程度更高。BRCA2突变的肿瘤具有特别高的甲基化程度。最后，通过利用基因表达数据，我们观察到大部分报告为具有亚型特异性表达模式的基因可能通过甲基化进行调控。我们已经发现基底样、管腔A和管腔B分子亚型的乳腺癌具有特异性甲基化谱。我们的研究结果表明，甲基化可能在乳腺癌的发展中发挥重要作用。
Five different molecular subtypes of breast cancer have been identified through gene expression profiling. Each subtype has a characteristic expression pattern suggested to partly depend on cellular origin. We aimed to investigate whether the molecular subtypes also display distinct methylation profiles. We analysed methylation status of 807 cancer-related genes in 189 fresh frozen primary breast tumours and four normal breast tissue samples using an array-based methylation assay. Unsupervised analysis revealed three groups of breast cancer with characteristic methylation patterns. The three groups were associated with the luminal A, luminal B and basal-like molecular subtypes of breast cancer, respectively, whereas cancers of the HER2-enriched and normal-like subtypes were distributed among the three groups. The methylation frequencies were significantly different between subtypes, with luminal B and basal-like tumours being most and least frequently methylated, respectively. Moreover, targets of the polycomb repressor complex in breast cancer and embryonic stem cells were more methylated in luminal B tumours than in other tumours. BRCA2-mutated tumours had a particularly high degree of methylation. Finally, by utilizing gene expression data, we observed that a large fraction of genes reported as having subtype-specific expression patterns might be regulated through methylation. We have found that breast cancers of the basal-like, luminal A and luminal B molecular subtypes harbour specific methylation profiles. Our results suggest that methylation may play an important role in the development of breast cancers.
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DOI：
10.1186/bcr2214
发表时间：
2008
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Pietersen AM;Horlings HM;Hauptmann M;Langerød A;Ajouaou A;Cornelissen-Steijger P;Wessels LF;Jonkers J;van de Vijver MJ;van Lohuizen M
通讯作者：
van Lohuizen M
影响因子：
64.8
作者：
通讯作者：
--
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：
64.5
作者：
Lee, TI;Jenner, RG;Young, RA
通讯作者：
Young, RA
影响因子：
30.8
作者：
Keshet, I;Schlesinger, Y;Simon, I
通讯作者：
Simon, I