Differential methylation relative to breast cancer subtype and matched normal tissue reveals distinct patterns.
Differential methylation relative to breast cancer subtype and matched normal tissue reveals distinct patterns.
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DOI：
10.1007/s10549-013-2738-0
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发表时间：
2013-11
影响因子：
3.8
通讯作者：
Swift-Scanlan, Theresa
中科院分区：
文献类型：
--
作者：
Bardowell, Sabrina A.;Parker, Joel;Fan, Cheng;Crandell, Jamie;Perou, Charles M.;Swift-Scanlan, Theresa
由于乳腺癌的异质性和单基因研究的广泛使用，对与分子亚型和临床特征相关的多基因、基因座特异性DNA甲基化模式的了解有限。因此，我们定量了140例乳腺肿瘤和匹配的正常组织中70个候选基因位点的DNA甲基化，并确定了与基因表达和肿瘤亚型的相关性。使用Sequenom的EpiTYPER平台，询问了大约1，200个CpG，并揭示了乳腺肿瘤相对于匹配的正常组织的六种DNA甲基化模式。在所有分子亚型中观察到几个基因位点的差异甲基化，而其他模式则依赖于亚型。许多基因位点的甲基化与基因表达呈负相关，在某些情况下，这种相关性仅在特定的乳腺肿瘤亚型中观察到。我们的研究结果在来自癌症基因组图谱数据集的更大的一组肿瘤和匹配的相邻正常组织上进行了验证，该数据集利用了来自Illumina Infinium 27和450 k阵列的甲基化数据。这些发现强调了在解释DNA甲基化结果时控制亚型的必要性，以及在不同基因区域询问多个CpG的重要性。本文的在线版本（doi：10.1007/s10549-013-2738-0）包含补充材料，可供授权用户使用。
Due to the heterogeneous nature of breast cancer and the widespread use of single-gene studies, there is limited knowledge of multi-gene, locus-specific DNA methylation patterns in relation to molecular subtype and clinical features. We, therefore, quantified DNA methylation of 70 candidate gene loci in 140 breast tumors and matched normal tissues and determined associations with gene expression and tumor subtype. Using Sequenom’s EpiTYPER platform, approximately 1,200 CpGs were interrogated and revealed six DNA methylation patterns in breast tumors relative to matched normal tissue. Differential methylation of several gene loci was observed within all molecular subtypes, while other patterns were subtype-dependent. Methylation of numerous gene loci was inversely correlated with gene expression, and in some cases, this correlation was only observed within specific breast tumor subtypes. Our findings were validated on a larger set of tumors and matched adjacent normal tissue from The Cancer Genome Atlas dataset, which utilized methylation data derived from both Illumina Infinium 27 and 450 k arrays. These findings highlight the need to control for subtype when interpreting DNA methylation results, and the importance of interrogating multiple CpGs across varied gene regions. The online version of this article (doi:10.1007/s10549-013-2738-0) contains supplementary material, which is available to authorized users.
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影响因子：
3.5
作者：
Baylin, SB;Esteller, M;Herman, JG
通讯作者：
Herman, JG
影响因子：
14.9
作者：
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影响因子：
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作者：
Suijkerbuijk, K. P. M.;Fackler, M. J.;van Diest, P. J.
通讯作者：
van Diest, P. J.
影响因子：
3.6
作者：
Swift-Scanlan, Theresa;Vang, Russell;Sukumar, Saraswati
通讯作者：
Sukumar, Saraswati