5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers.
5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers.
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DOI：
10.1038/cr.2017.121
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发表时间：
2017-10
期刊：
影响因子：
44.1
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Li W;Zhang X;Lu X;You L;Song Y;Luo Z;Zhang J;Nie J;Zheng W;Xu D;Wang Y;Dong Y;Yu S;Hong J;Shi J;Hao H;Luo F;Hua L;Wang P;Qian X;Yuan F;Wei L;Cui M;Zhang T;Liao Q;Dai M;Liu Z;Chen G;Meckel K;Adhikari S;Jia G;Bissonnette MB;Zhang X;Zhao Y;Zhang W;He C;Liu J
DNA修饰，如5-甲基胞嘧啶(5mC)和5-羟甲基胞嘧啶(5hmC)是已知的影响哺乳动物全球基因表达的表观遗传标记。鉴于它们普遍存在于人类基因组中，与基因表达密切相关，且化学稳定性高，这些DNA表观遗传标记可能成为癌症诊断的理想生物标志物。利用一种高灵敏度和选择性的化学标记技术，我们报道了从260例新近诊断为结直肠癌、胃癌、胰腺癌、肝癌或甲状腺癌的患者和90名健康人的正常组织中收集的成对肿瘤和邻近组织的循环无细胞DNA(CfDNA)和基因组DNA(GDNA)中的5HmC的全基因组图谱。5hmC主要分布在与开放染色质和允许的组蛋白修饰一致的转录活性区域。在cfDNA中发现了与癌症相关的强大的5hmC信号，这是特定癌症类型的特征。基于循环cfDNA的5hmC生物标志物对结直肠癌和胃癌的预测性很高，优于传统的生物标记物，与组织活检的5hmC生物标记物相当。因此，这一新的策略可能导致开发有效的、微创的方法来诊断和预测血液样本中的癌症预后。
DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA (cfDNA) and in genomic DNA (gDNA) of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver or thyroid cancer and normal tissues from 90 healthy individuals. 5hmC was mainly distributed in transcriptionally active regions coincident with open chromatin and permissive histone modifications. Robust cancer-associated 5hmC signatures were identified in cfDNA that were characteristic for specific cancer types. 5hmC-based biomarkers of circulating cfDNA were highly predictive of colorectal and gastric cancers and were superior to conventional biomarkers and comparable to 5hmC biomarkers from tissue biopsies. Thus, this new strategy could lead to the development of effective, minimally invasive methods for diagnosis and prognosis of cancer from the analyses of blood samples.
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影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
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Hubbard TJ
影响因子：
7.8
作者：
Jones MJ;Goodman SJ;Kobor MS
通讯作者：
Kobor MS
影响因子：
24.5
作者：
Church TR;Wandell M;Lofton-Day C;Mongin SJ;Burger M;Payne SR;Castaños-Vélez E;Blumenstein BA;Rösch T;Osborn N;Snover D;Day RW;Ransohoff DF;PRESEPT Clinical Study Steering Committee, Investigators and Study Team
通讯作者：
PRESEPT Clinical Study Steering Committee, Investigators and Study Team
影响因子：
21.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Guo JU;Su Y;Zhong C;Ming GL;Song H
通讯作者：
Song H