A panel of genes methylated with high frequency in colorectal cancer.
A panel of genes methylated with high frequency in colorectal cancer.
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DOI：
10.1186/1471-2407-14-54
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发表时间：
2014-01-31
期刊：
影响因子：
3.8
通讯作者：
Molloy PL
中科院分区：
文献类型：
--
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
结直肠癌的发展伴随着广泛的表观遗传学变化，包括频繁的区域高甲基化，特别是基因启动子区。包括SEPT9、VIM1和TMEFF2在内的特定基因在高比例的癌症中发生甲基化，目前正在开发检测血液和/或粪便样本中癌症来源的甲基化DNA序列的诊断方法。有相当大的潜力开发新的DNA甲基化生物标记物或面板，以提高目前癌症检测测试的敏感性和特异性。结合表观基因组学方法-DNA去甲基化处理后大肠癌细胞系中基因表达的激活，以及两种新的全基因组甲基化评估方法-被用来确定在高比例的CRC中甲基化的候选基因。用罗氏454测序法对匹配的结直肠癌组织、非肿瘤组织和健康供者外周血经亚硫酸氢盐处理的DNA进行多重扩增产物测序。用定量甲基化特异性聚合酶链式反应(QMSP)检测大肠组织和血液中DNA甲基化水平。联合分析确定了42个候选基因作为DNA甲基化生物标志物进行评估。在10个匹配的肿瘤/正常组织样本中，通过多重亚硫酸氢盐测序，确定了其中24个基因的DNA甲基化特征；其中23个基因在结直肠癌中被证实存在差异甲基化。建立了32个基因的qMSP分析，其中包括15个测序基因，并用于量化肿瘤、腺瘤和非肿瘤性结直肠组织以及健康供者外周血中的甲基化。这32个基因中的24个在50%的肿瘤样本中发生甲基化，其中11个基因在80%或更多的癌组织和类似比例的腺瘤中发生甲基化。这项研究描述了一组23个基因的特征，这些基因显示50%的结直肠癌组织中DNA甲基化水平高于非肿瘤组织。其中6个基因(SOX21、SLC6A15、NPY、GRASH、ST8SIA1和ZSCAN18)在非肿瘤性大肠组织中甲基化水平很低，是粪便检测的候选生物标志物，而11个基因(BCAT1、COL4A2、DLX5、FGF5、FOXF1、FOXI2、GRASP、IKZF1、IRF4、SDC2和SOX21)外周血DNA甲基化水平很低，适合作为血液诊断标志物进行进一步评估。
The development of colorectal cancer (CRC) is accompanied by extensive epigenetic changes, including frequent regional hypermethylation particularly of gene promoter regions. Specific genes, including SEPT9, VIM1 and TMEFF2 become methylated in a high fraction of cancers and diagnostic assays for detection of cancer-derived methylated DNA sequences in blood and/or fecal samples are being developed. There is considerable potential for the development of new DNA methylation biomarkers or panels to improve the sensitivity and specificity of current cancer detection tests. Combined epigenomic methods – activation of gene expression in CRC cell lines following DNA demethylating treatment, and two novel methods of genome-wide methylation assessment – were used to identify candidate genes methylated in a high fraction of CRCs. Multiplexed amplicon sequencing of PCR products from bisulfite-treated DNA of matched CRC and non-neoplastic tissue as well as healthy donor peripheral blood was performed using Roche 454 sequencing. Levels of DNA methylation in colorectal tissues and blood were determined by quantitative methylation specific PCR (qMSP). Combined analyses identified 42 candidate genes for evaluation as DNA methylation biomarkers. DNA methylation profiles of 24 of these genes were characterised by multiplexed bisulfite-sequencing in ten matched tumor/normal tissue samples; differential methylation in CRC was confirmed for 23 of these genes. qMSP assays were developed for 32 genes, including 15 of the sequenced genes, and used to quantify methylation in tumor, adenoma and non-neoplastic colorectal tissue and from healthy donor peripheral blood. 24 of the 32 genes were methylated in >50% of neoplastic samples, including 11 genes that were methylated in 80% or more CRCs and a similar fraction of adenomas. This study has characterised a panel of 23 genes that show elevated DNA methylation in >50% of CRC tissue relative to non-neoplastic tissue. Six of these genes (SOX21, SLC6A15, NPY, GRASP, ST8SIA1 and ZSCAN18) show very low methylation in non-neoplastic colorectal tissue and are candidate biomarkers for stool-based assays, while 11 genes (BCAT1, COL4A2, DLX5, FGF5, FOXF1, FOXI2, GRASP, IKZF1, IRF4, SDC2 and SOX21) have very low methylation in peripheral blood DNA and are suitable for further evaluation as blood-based diagnostic markers.
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影响因子：
3.8
作者：
Ang PW;Loh M;Liem N;Lim PL;Grieu F;Vaithilingam A;Platell C;Yong WP;Iacopetta B;Soong R
通讯作者：
Soong R
影响因子：
7
作者：
Hinoue, Toshinori;Weisenberger, Daniel J.;Laird, Peter W.
通讯作者：
Laird, Peter W.
影响因子：
2.7
作者：
Kibriya MG;Raza M;Jasmine F;Roy S;Paul-Brutus R;Rahaman R;Dodsworth C;Rakibuz-Zaman M;Kamal M;Ahsan H
通讯作者：
Ahsan H
影响因子：
3.7
作者：
Kim YH;Lee HC;Kim SY;Yeom YI;Ryu KJ;Min BH;Kim DH;Son HJ;Rhee PL;Kim JJ;Rhee JC;Kim HC;Chun HK;Grady WM;Kim YS
通讯作者：
Kim YS
影响因子：
3.7
作者：
Lange CP;Campan M;Hinoue T;Schmitz RF;van der Meulen-de Jong AE;Slingerland H;Kok PJ;van Dijk CM;Weisenberger DJ;Shen H;Tollenaar RA;Laird PW
通讯作者：
Laird PW