Promoter methylation correlates with reduced NDRG2 expression in advanced colon tumour.
Promoter methylation correlates with reduced NDRG2 expression in advanced colon tumour.
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DOI：
10.1186/1755-8794-2-11
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发表时间：
2009-03-03
影响因子：
2.7
通讯作者：
Andriulli A
中科院分区：
文献类型：
--
作者：
Piepoli A;Cotugno R;Merla G;Gentile A;Augello B;Quitadamo M;Merla A;Panza A;Carella M;Maglietta R;D'Addabbo A;Ancona N;Fusilli S;Perri F;Andriulli A
癌症相关基因CpG岛的异常甲基化是癌症发生中最早和最常见的改变之一，可能对癌症诊断或评估复发性疾病具有价值。这种机制通常导致肿瘤抑制基因的失活。我们设计了目前的研究，以验证我们以前的微阵列数据，并确定新的高甲基化基因启动子。通过定量逆转录聚合酶链反应分析，在不同的8例结直肠癌（CRC）患者中进行验证试验。比较3个CRC细胞系在5-氮杂-2 '-脱氧胞苷处理前后的差异RNA表达谱，以鉴定高甲基化基因。通过亚硫酸氢盐基因组测序和甲基化特异性聚合酶链反应（MSP）在3个细胞系和30例CRC患者的肿瘤组织中评价这些基因的DNA甲基化状态。我们之前的基因组搜索数据在新的8例CRC患者中得到了证实。在该验证组中，六个基因在三个CRC细胞系中的至少两个中显示出药物处理后的高诱导。其中，N-myc下游调节基因2（NDRG 2）启动子在所有CRC细胞系中被发现甲基化。NDRG 2高甲基化也在30例原发性CRC组织中的8例（27%）中检测到，并且与晚期AJCC IV期显著相关。正常结肠组织未发生甲基化。这些发现强调了结合基因表达模式和表观遗传数据来识别肿瘤生物标志物的有用性，并表明NDRG 2沉默可能对肿瘤侵袭性产生影响，与更晚期阶段相关。
Aberrant DNA methylation of CpG islands of cancer-related genes is among the earliest and most frequent alterations in cancerogenesis and might be of value for either diagnosing cancer or evaluating recurrent disease. This mechanism usually leads to inactivation of tumour-suppressor genes. We have designed the current study to validate our previous microarray data and to identify novel hypermethylated gene promoters. The validation assay was performed in a different set of 8 patients with colorectal cancer (CRC) by means quantitative reverse-transcriptase polymerase chain reaction analysis. The differential RNA expression profiles of three CRC cell lines before and after 5-aza-2'-deoxycytidine treatment were compared to identify the hypermethylated genes. The DNA methylation status of these genes was evaluated by means of bisulphite genomic sequencing and methylation-specific polymerase chain reaction (MSP) in the 3 cell lines and in tumour tissues from 30 patients with CRC. Data from our previous genome search have received confirmation in the new set of 8 patients with CRC. In this validation set six genes showed a high induction after drug treatment in at least two of three CRC cell lines. Among them, the N-myc downstream-regulated gene 2 (NDRG2) promoter was found methylated in all CRC cell lines. NDRG2 hypermethylation was also detected in 8 out of 30 (27%) primary CRC tissues and was significantly associated with advanced AJCC stage IV. Normal colon tissues were not methylated. The findings highlight the usefulness of combining gene expression patterns and epigenetic data to identify tumour biomarkers, and suggest that NDRG2 silencing might bear influence on tumour invasiveness, being associated with a more advanced stage.
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DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
3.8
作者：
Lorentzen A;Vogel LK;Lewinsky RH;Saebø M;Skjelbred CF;Godiksen S;Hoff G;Tveit KM;Lothe IM;Ikdahl T;Kure EH;Mitchelmore C
通讯作者：
Mitchelmore C
影响因子：
4.8
作者：
Burchfield, JG;Lennard, AJ;Schmitz-Peiffer, C
通讯作者：
Schmitz-Peiffer, C
影响因子：
3
作者：
Ancona, N.;Maglietta, R.;Perri, F.
通讯作者：
Perri, F.
影响因子：
45.3
作者：
Benson, AB;Schrag, D;Haller, DG
通讯作者：
Haller, DG