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使用平铺阵列检测表观遗传改变。

Detection of epigenetic alterations using tiling arrays.

作者信息

Cheung Hoi-Hung, Rennert Owen M, Lee Tin-Lap

机构信息

Laboratory of Clinical and Developmental Genomics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

出版信息

Methods Mol Biol. 2013;1067:79-86. doi: 10.1007/978-1-62703-607-8_6.

Abstract

The epigenetic status of cancer cells is a consequence of the neoplastic transformation of their normal counterpart. Epigenetic changes directly influence gene expression and chromatin organization, which consequently leads to escape from the tumor-suppression mechanisms. Global mapping for specific epigenetic modifications (e.g., DNA methylation) of the entire genome is required to reveal epigenetic hotspots associated with a cancer type/stage. DNA tiling arrays may be applied for genome-wide analysis of different epigenetic marks. Tiling arrays are high-density DNA microarrays that can be custom-made to survey regions of interest (e.g., gene promoters) or permit whole-genome analysis. To identify the genomic alterations associated with testicular cancers we used tiling arrays to profile their methylome. We successfully identified numerous epigenetically modified loci that arose as a consequence of tumor progression.

摘要

癌细胞的表观遗传状态是其正常对应细胞发生肿瘤转化的结果。表观遗传变化直接影响基因表达和染色质组织,进而导致肿瘤抑制机制失效。需要对整个基因组进行特定表观遗传修饰(如DNA甲基化)的全局图谱绘制,以揭示与癌症类型/阶段相关的表观遗传热点。DNA平铺阵列可用于全基因组范围内不同表观遗传标记的分析。平铺阵列是高密度DNA微阵列,可定制以检测感兴趣的区域(如基因启动子)或进行全基因组分析。为了识别与睾丸癌相关的基因组改变,我们使用平铺阵列对其甲基化组进行分析。我们成功地鉴定出了许多因肿瘤进展而产生的表观遗传修饰位点。

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