Viral driven epigenetic events alter the expression of cancer-related genes in Epstein-Barr-virus naturally infected Burkitt lymphoma cell lines.
Viral driven epigenetic events alter the expression of cancer-related genes in Epstein-Barr-virus naturally infected Burkitt lymphoma cell lines.
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DOI：
10.1038/s41598-017-05713-2
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发表时间：
2017-07-19
影响因子：
4.6
通讯作者：
Accardi R
中科院分区：
文献类型：
--
作者：
Hernandez-Vargas H;Gruffat H;Cros MP;Diederichs A;Sirand C;Vargas-Ayala RC;Jay A;Durand G;Le Calvez-Kelm F;Herceg Z;Manet E;Wild CP;Tommasino M;Accardi R
EB病毒（EBV）被鉴定为第一种与人类恶性肿瘤伯基特淋巴瘤（BL）相关的人类病毒，伯基特淋巴瘤是撒哈拉以南非洲的一种儿科癌症。EBV如何促进淋巴瘤发生的确切机制尚未完全了解。最近的研究强调了地方性（EBV+）和散发性（EBV−）BL之间的遗传差异，地方性变异体显示出较低的体细胞突变负荷，这表明在地方性BL的发病机制中涉及另一种病毒驱动的转化过程。我们检验了以下假设：EBV感染可能诱导DNA甲基化的整体变化，从而可能解释了在地方性BL中观察到的较低突变负荷。我们对一组BL衍生的细胞系（自然感染或未感染EBV）的甲基化谱进行了比较分析，结果显示病毒的存在与特定的DNA甲基化模式相关，导致细胞基因表达改变，这些基因在淋巴瘤发生中具有已知或潜在的作用。这些包括ID3，一个经常在散发性BL中发现突变的基因。总之，本研究提供的证据表明，EB病毒可能有助于通过表观遗传机制的BL的发病机制。
Epstein-Barr virus (EBV) was identified as the first human virus to be associated with a human malignancy, Burkitt’s lymphoma (BL), a pediatric cancer endemic in sub-Saharan Africa. The exact mechanism of how EBV contributes to the process of lymphomagenesis is not fully understood. Recent studies have highlighted a genetic difference between endemic (EBV+) and sporadic (EBV−) BL, with the endemic variant showing a lower somatic mutation load, which suggests the involvement of an alternative virally-driven process of transformation in the pathogenesis of endemic BL. We tested the hypothesis that a global change in DNA methylation may be induced by infection with EBV, possibly thereby accounting for the lower mutation load observed in endemic BL. Our comparative analysis of the methylation profiles of a panel of BL derived cell lines, naturally infected or not with EBV, revealed that the presence of the virus is associated with a specific pattern of DNA methylation resulting in altered expression of cellular genes with a known or potential role in lymphomagenesis. These included ID3, a gene often found to be mutated in sporadic BL. In summary this study provides evidence that EBV may contribute to the pathogenesis of BL through an epigenetic mechanism.
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