Evaluation of Methylation Biomarkers for Detection of Circulating Tumor DNA and Application to Colorectal Cancer.
Evaluation of Methylation Biomarkers for Detection of Circulating Tumor DNA and Application to Colorectal Cancer.
复制标题
DOI：
10.3390/genes7120125
复制
发表时间：
2016-12-15
期刊：
影响因子：
3.5
通讯作者：
Molloy PL
中科院分区：
文献类型：
--
作者：
Mitchell SM;Ho T;Brown GS;Baker RT;Thomas ML;McEvoy A;Xu ZZ;Ross JP;Lockett TJ;Young GP;LaPointe LC;Pedersen SK;Molloy PL
实体瘤将DNA脱落到循环中，越来越多的证据表明，循环肿瘤DNA（ctDNA）的检测具有广泛的临床用途，包括监测疾病、预后、对化疗的反应和跟踪肿瘤异质性。从血浆或血清分离的循环无细胞DNA（ccfDNA）中ctDNA的出现通常通过鉴定肿瘤特异性特征如插入、缺失、突变和/或异常甲基化来检测。甲基化是正常的细胞调节事件，并且由于大多数ccfDNA来源于白色血细胞（WBC），因此重要的是肿瘤特异性DNA甲基化标志物在WBC DNA中显示罕见至无甲基化事件。我们使用了一种新的方法来评估WBC DNA中低水平的DNA甲基化。在WBC DNA中分析了29个先前鉴定的区域（存在于17个基因中）中的DNA甲基化，并使用甲基化特异性PCR测定法在临床样品中检测了8个差异甲基化区域（DMR）。BCAT 1、GRASP、IKZF 1和IRF 4基因的DMR在结肠镜检查证实的健康受试者血浆中表现出低阳性，为3.5%至7%，结肠镜检查证实的结直肠癌患者ctDNA检测的灵敏度分别为65%、54.5%、67.6%和59%。
Solid tumors shed DNA into circulation, and there is growing evidence that the detection of circulating tumor DNA (ctDNA) has broad clinical utility, including monitoring of disease, prognosis, response to chemotherapy and tracking tumor heterogeneity. The appearance of ctDNA in the circulating cell-free DNA (ccfDNA) isolated from plasma or serum is commonly detected by identifying tumor-specific features such as insertions, deletions, mutations and/or aberrant methylation. Methylation is a normal cell regulatory event, and since the majority of ccfDNA is derived from white blood cells (WBC), it is important that tumour-specific DNA methylation markers show rare to no methylation events in WBC DNA. We have used a novel approach for assessment of low levels of DNA methylation in WBC DNA. DNA methylation in 29 previously identified regions (residing in 17 genes) was analyzed in WBC DNA and eight differentially-methylated regions (DMRs) were taken through to testing in clinical samples using methylation specific PCR assays. DMRs residing in four genes, BCAT1, GRASP, IKZF1 and IRF4, exhibited low positivity, 3.5% to 7%, in the plasma of colonoscopy-confirmed healthy subjects, with the sensitivity for detection of ctDNA in colonoscopy-confirmed patients with colorectal cancer being 65%, 54.5%, 67.6% and 59% respectively.
登录
查看更多内容
影响因子：
30.8
作者：
Kulis M;Merkel A;Heath S;Queirós AC;Schuyler RP;Castellano G;Beekman R;Raineri E;Esteve A;Clot G;Verdaguer-Dot N;Duran-Ferrer M;Russiñol N;Vilarrasa-Blasi R;Ecker S;Pancaldi V;Rico D;Agueda L;Blanc J;Richardson D;Clarke L;Datta A;Pascual M;Agirre X;Prosper F;Alignani D;Paiva B;Caron G;Fest T;Muench MO;Fomin ME;Lee ST;Wiemels JL;Valencia A;Gut M;Flicek P;Stunnenberg HG;Siebert R;Küppers R;Gut IG;Campo E;Martín-Subero JI
通讯作者：
Martín-Subero JI
影响因子：
64.8
作者：
Schultz, Matthew D.;He, Yupeng;Whitaker, John W.;Hariharan, Manoj;Mukamel, Eran A.;Leung, Danny;Rajagopal, Nisha;Nery, Joseph R.;Urich, Mark A.;Chen, Huaming;Lin, Shin;Lin, Yiing;Jung, Inkyung;Schmitt, Anthony D.;Selvaraj, Siddarth;Ren, Bing;Sejnowski, Terrence J.;Wang, Wei;Ecker, Joseph R.
通讯作者：
Ecker, Joseph R.
影响因子：
16.6
作者：
Stirzaker, Clare;Zotenko, Elena;Clark, Susan J.
通讯作者：
Clark, Susan J.
DOI：
10.1016/j.mrfmmm.2016.02.001
发表时间：
2016-04-01
影响因子：
2.3
作者：
Marcinkowska-Swojak, Malgorzata;Handschuh, Luiza;Kozlowski, Piotr
通讯作者：
Kozlowski, Piotr
影响因子：
3.8
作者：
Mitchell SM;Ross JP;Drew HR;Ho T;Brown GS;Saunders NF;Duesing KR;Buckley MJ;Dunne R;Beetson I;Rand KN;McEvoy A;Thomas ML;Baker RT;Wattchow DA;Young GP;Lockett TJ;Pedersen SK;Lapointe LC;Molloy PL
通讯作者：
Molloy PL