Sanford-Burnham Medical Research Institute, Orlando FL 32827 USA.
Sci Rep. 2013 Oct 16;3:2962. doi: 10.1038/srep02962.
Metastatic melanoma is a malignant cancer with generally poor prognosis, with no targeted chemotherapy. To identify epigenetic changes related to melanoma, we have determined genome-wide methylated CpG island distributions by next-generation sequencing. Melanoma chromosomes tend to be differentially methylated over short CpG island tracts. CpG islands in the upstream regulatory regions of many coding and noncoding RNA genes, including, for example, TERC, which encodes the telomerase RNA, exhibit extensive hypermethylation, whereas several repeated elements, such as LINE 2, and several LTR elements, are hypomethylated in advanced stage melanoma cell lines. By using CpG island demethylation profiles, and by integrating these data with RNA-seq data obtained from melanoma cells, we have identified a co-expression network of differentially methylated genes with significance for cancer related functions. Focused assays of melanoma patient tissue samples for CpG island methylation near the noncoding RNA gene SNORD-10 demonstrated high specificity.
转移性黑色素瘤是一种恶性癌症，预后通常较差，目前尚无靶向化疗药物。为了鉴定与黑色素瘤相关的表观遗传变化，我们通过下一代测序确定了全基因组甲基化 CpG 岛分布。黑色素瘤染色体在短 CpG 岛片段上往往表现出不同程度的甲基化。许多编码和非编码 RNA 基因的上游调控区域中的 CpG 岛，例如编码端粒酶 RNA 的 TERC，表现出广泛的超甲基化，而几个重复元件，如 LINE2 和几个 LTR 元件，在晚期黑色素瘤细胞系中则呈低甲基化状态。通过使用 CpG 岛去甲基化谱，并将这些数据与从黑色素瘤细胞获得的 RNA-seq 数据整合，我们鉴定了具有癌症相关功能意义的差异甲基化基因的共表达网络。对黑色素瘤患者组织样本中非编码 RNA 基因 SNORD-10 附近的 CpG 岛甲基化进行的焦点分析显示出高度特异性。
