5-Hydroxymethylcytosine is strongly depleted in human cancers but its levels do not correlate with IDH1 mutations.
5-Hydroxymethylcytosine is strongly depleted in human cancers but its levels do not correlate with IDH1 mutations.
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DOI：
10.1158/0008-5472.can-11-2023
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发表时间：
2011-12-15
期刊：
影响因子：
11.2
通讯作者：
Pfeifer GP
中科院分区：
文献类型：
--
作者：
Jin SG;Jiang Y;Qiu R;Rauch TA;Wang Y;Schackert G;Krex D;Lu Q;Pfeifer GP
碱基5-羟甲基胞嘧啶（5 hmC）是哺乳动物DNA中5-甲基胞嘧啶（5 mC）的氧化产物。在此，我们使用灵敏和定量的方法来评估基因组DNA中5-羟甲基-2 ′-脱氧胞苷（5 hmdC）和5-甲基-2 ′-脱氧胞苷（5 mdC）的水平，研究5 hmC的水平是否可以区分正常组织和肿瘤组织。在鳞状细胞肺癌中，与正常肺组织相比，5 hmdC的水平基本上被耗尽，降低高达5倍。在脑肿瘤中，5 hmdC显示出甚至更剧烈的降低，其水平比正常脑中低多达30倍，但5 hmdC水平与异柠檬酸脱氢酶-1（IDH 1）的突变无关。此外，免疫组织化学分析表明，5 hmC在许多类型的人类癌症中显著缺失。重要的是，在增殖细胞中缺乏5 hmC的情况下，观察到5 hmC水平与细胞增殖之间的负相关。因此，这些数据表明，5 hmdC在人类恶性肿瘤中被强烈耗尽，这一发现为癌症组织中发现的异常表观基因组增加了另一层复杂性。此外，5 hmC的缺乏可能成为癌症诊断的有用生物标志物。
The base 5-hydroxymethylcytosine (5hmC) was recently identified as an oxidation product of 5-methylcytosine (5mC) in mammalian DNA. Here, using sensitive and quantitative methods to assess levels of 5-hydroxymethyl-2′-deoxycytidine (5hmdC) and 5-methyl-2′-deoxycytidine (5mdC) in genomic DNA, we investigated whether levels of 5hmC can distinguish normal tissue from tumor tissue. In squamous cell lung cancers, levels of 5hmdC were depleted substantially with up to 5-fold reduction compared to normal lung tissue. In brain tumors, 5hmdC showed an even more drastic reduction with levels up to >30-fold lower than in normal brain, but 5hmdC levels were independent of mutations in isocitrate dehydrogenase-1 (IDH1). Furthermore, immunohistochemical analysis indicated that 5hmC is remarkably depleted in many types of human cancer. Importantly, an inverse relationship between 5hmC levels and cell proliferation was observed with lack of 5hmC in proliferating cells. The data therefore suggest that 5hmdC is strongly depleted in human malignant tumors, a finding that adds another layer of complexity to the aberrant epigenome found in cancer tissue. In addition, a lack of 5hmC may become a useful biomarker for cancer diagnosis.