胞嘧啶甲基化有助于哺乳动物基因表达和正常造血的调节。它由 DNA 甲基转移酶家族（包括 DNMT1、DNMT3A 和 DNMT3B）催化。外周 T 细胞淋巴瘤 (PTCL) 代表侵袭性成熟 T 细胞恶性肿瘤，表现出广泛的临床特征，预后不良，分子病理学了解不足。为了更好地了解分子格局并识别参与疾病维持的候选基因，我们对 PTCL 的 DNA 甲基化和基因表达进行了分析。我们发现 PTCL 中的甲基化模式失调且异质，但在所有样本中共有 767 个低甲基化和 567 个高甲基化差异甲基化区域 (DMR)，以及 231 个基因上调和 91 个基因下调，这表明与肿瘤发展存在潜在关联。我们进一步鉴定了 39 个与大多数 PTCL 基因表达增加相关的低甲基化启动子。这种假定的致癌特征包括 TRIP13（甲状腺激素受体相互作用蛋白 13）基因，该基因的遗传和药理学失活可通过诱导 G2-M 停滞和细胞凋亡来抑制 T 细胞系的增殖。因此，我们的数据表明，人类 PTCL 具有大量反复出现的甲基化改变，这些改变可能会影响对增殖至关重要的基因的表达，而这些基因的靶向可能有利于抗淋巴瘤治疗。

Cytosine methylation contributes to the regulation of gene expression and normal hematopoiesis in mammals. It is catalyzed by the family of DNA methyltransferases that include DNMT1, DNMT3A, and DNMT3B. Peripheral T-cell lymphomas (PTCLs) represent aggressive mature T-cell malignancies exhibiting a broad spectrum of clinical features with poor prognosis and inadequately understood molecular pathobiology. To better understand the molecular landscape and identify candidate genes involved in disease maintenance, we profiled DNA methylation and gene expression of PTCLs. We found that the methylation patterns in PTCLs are deregulated and heterogeneous but share 767 hypo- and 567 hypermethylated differentially methylated regions (DMRs) along with 231 genes up- and 91 genes downregulated in all samples, suggesting a potential association with tumor development. We further identified 39 hypomethylated promoters associated with increased gene expression in the majority of PTCLs. This putative oncogenic signature included the TRIP13 (thyroid hormone receptor interactor 13) gene whose genetic and pharmacologic inactivation inhibited the proliferation of T-cell lines by inducing G2-M arrest and apoptosis. Our data thus show that human PTCLs have a significant number of recurrent methylation alterations that may affect the expression of genes critical for proliferation whose targeting might be beneficial in anti-lymphoma treatments.