Cheung Hoi-Hung, Rennert Owen M, Lee Tin-Lap
Laboratory of Clinical and Developmental Genomics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Methods Mol Biol. 2013;1067:79-86. doi: 10.1007/978-1-62703-607-8_6.
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.
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。
