DNA methylation is a comprehensively studied epigenetic modification and plays crucial roles in cancer development. In the present study, MethylCap-seq was used to characterize the genome-wide DNA methylation patterns in canine high-grade B-cell lymphoma (cHGBL). Canine methylated DNA fragments were captured and the MEDIUM-HIGH and LOW fraction of methylated DNA was obtained based on variation in CpG methylation density. In the MEDIUM-HIGH and LOW fraction, 2144 and 1987 cHGBL-specific hypermethylated genes, respectively, were identified. Functional analysis highlighted pathways strongly related to oncogenesis. The relevant signaling pathways associated with neuronal system were also revealed, echoing recent novel findings that neurogenesis plays key roles in tumor establishment. In addition, 14 genes were hypermethylated in all the cHGBL cases but not in the healthy dogs. These genes might be potential signatures for tracing cHGBL, and some of them have been reported to play roles in various types of cancers. Further, the distinct methylation pattern of cHGBL showed a concordance with the clinical outcome, suggesting that aberrant epigenetic changes may influence tumor behavior. In summary, our study characterized genome-wide DNA methylation patterns using MethylCap-seq in cHGBL; the findings suggest that specific DNA hypermethylation holds promise for dissecting tumorigenesis and uncovering biomarkers for monitoring the progression of cHGBL.

中文翻译：

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在犬高级别 B 细胞淋巴瘤中使用 MethylCap-seq 进行全基因组 DNA 甲基化分析

DNA 甲基化是一种经过全面研究的表观遗传修饰，在癌症发展中起着至关重要的作用。在本研究中，MethylCap-seq 用于表征犬高级别 B 细胞淋巴瘤 (cHGBL) 的全基因组 DNA 甲基化模式。捕获犬甲基化 DNA 片段，并根据 CpG 甲基化密度的变化获得甲基化 DNA 的中高和低部分。在 MEDIUM-HIGH 和 LOW 级分中，分别鉴定了 2144 个和 1987 个 cHGBL 特异性高甲基化基因。功能分析强调了与肿瘤发生密切相关的途径。还揭示了与神经元系统相关的相关信号通路，这与最近神经发生在肿瘤形成中起关键作用的新发现相呼应。此外，14 个基因在所有 cHGBL 病例中都发生了高甲基化，但在健康犬中没有。这些基因可能是追踪 cHGBL 的潜在特征，据报道，其中一些基因在各种类型的癌症中发挥作用。此外，cHGBL 的独特甲基化模式与临床结果一致，表明异常的表观遗传变化可能会影响肿瘤行为。总之，我们的研究在 cHGBL 中使用 MethylCap-seq 表征了全基因组 DNA 甲基化模式；研究结果表明，特定的 DNA 高甲基化有望用于剖析肿瘤发生并发现用于监测 cHGBL 进展的生物标志物。cHGBL 的独特甲基化模式与临床结果一致，表明异常的表观遗传变化可能影响肿瘤行为。总之，我们的研究在 cHGBL 中使用 MethylCap-seq 表征了全基因组 DNA 甲基化模式；研究结果表明，特定的 DNA 高甲基化有望用于剖析肿瘤发生并发现用于监测 cHGBL 进展的生物标志物。cHGBL 的独特甲基化模式与临床结果一致，表明异常的表观遗传变化可能影响肿瘤行为。总之，我们的研究在 cHGBL 中使用 MethylCap-seq 表征了全基因组 DNA 甲基化模式；研究结果表明，特定的 DNA 高甲基化有望用于剖析肿瘤发生并发现用于监测 cHGBL 进展的生物标志物。