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Filtrating colorectal cancer associated genes by integrated analyses of global DNA methylation and hydroxymethylation in cancer and normal tissue

机译:通过综合分析癌症和正常组织中的整体DNA甲基化和羟甲基化来过滤结直肠癌相关基因

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Recently, 5-hydroxymethylcytosine patterning across the tumor genome was considered as a hallmark of cancer development and progression. However, locus-specific difference of hydroxymethylation between colorectal cancer and normal tissue is unknown. In this study, we performed a newly developed method, HMST-seq, to profile 726 aberrant methylated loci and 689 aberrant hydroxymethylated loci synchronously in genome wide of colorectal cancers, majority of which presented higher methylation or lower hydroxymethylationin than in normal group. Besides, abnormal hydroxymethylated modification was more frequently occur at proximal regions close to TSSs and TSSs regions than abnormal methylation. Subsequently, we screened four genes (ALOX15, GHRHR, TFPI2 and TKTL1) with aberrant methylation and aberrant hydroxymethylation at some genome position by functional enrichment analysis as candidate genes associated with colorectal cancer. Our results may allow us to select differentially epigenetically modified target genes implicated in colorectal cancer tumorigenesis.
机译:最近,整个肿瘤基因组中的5-羟甲基胞嘧啶模式被认为是癌症发展和进展的标志。然而,大肠癌和正常组织之间羟甲基化的基因座特异性差异尚不清楚。在这项研究中,我们进行了一项新开发的方法HMST-seq,以在大肠癌基因组范围内同步分析726个异常甲基化基因座和689个异常羟甲基化基因座,其中大多数基因组的甲基化程度较高或低于正常组。此外,与甲基化异常相比,在接近TSS和TSSs区域的近端区域更经常发生异常的羟甲基化修饰。随后,我们通过功能富集分析筛选了四个基因(ALOX15,GHHRR,TFPI2和TKTL1)在某些基因组位置具有异常甲基化和羟基甲基化异常,作为与大肠癌相关的候选基因。我们的结果可能使我们能够选择与大肠癌肿瘤发生有关的差异表观遗传修饰的靶基因。

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