DNA methylation biomarker candidates for early detection of colon cancer.

DNA methylation biomarker candidates for early detection of colon cancer.
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DOI:
10.1007/s13277-011-0302-2
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发表时间:
2012-04
期刊:
影响因子:
--
通讯作者:
Ahuja, Nita
Ahuja, Nita
中科院分区:
其他
文献类型:
--
作者:
Yi, Joo Mi;Dhir, Mashaal;Guzzetta, Angela A.;Iacobuzio-Donahue, Christine A.;Heo, Kyu;Yang, Kwang Mo;Suzuki, Hiromu;Toyota, Minoru;Kim, Hwan-Mook;Ahuja, Nita

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肿瘤抑制基因的启动子CpG岛超甲基化是所有人类癌症的共同标志。许多研究人员一直在寻找潜在的表观遗传治疗癌症的基因表达谱与DNA微阵列的方法。我们最近在结直肠癌(CRC)细胞系中的CpG岛超甲基化和基因表达的全基因组平台显示,FBN2和TCERG1L基因沉默与启动子区域中CpG岛的DNA超甲基化相关。在这项研究中,结直肠癌中FBN2和TCERG1L的启动子DNA超甲基化作为结直肠癌的早期和癌症特异性事件发生。两种基因在结肠癌细胞系(两种基因>80%)、腺瘤(FBN2为77%,TCERG1L为90%,n=39)和癌(FBN2为86%,TCERG1L为99%,n=124)中均显示出高频率的甲基化。亚硫酸氢盐测序证实了结肠癌细胞系和癌症中FBN2和TCERG1L启动子的癌症特异性甲基化,但在正常结肠中没有。FBN2和TCERG1L的甲基化伴随着细胞系和原发性肿瘤中的下调,如Oncomine™网站中所述。总之,我们的研究结果表明,FBN2和TCERG1L的基因沉默与结直肠癌肿瘤中启动子DNA超甲基化相关,可能是早期检测结直肠癌的极好生物标志物。
Promoter CpG island hypermethylation of tumor suppressor genes is a common hallmark of all human cancers. Many researchers have been looking for potential epigenetic therapeutic targets in cancer using gene expression profiling with DNA microarray approaches. Our recent genome-wide platform of CpG island hypermethylation and gene expression in colorectal cancer (CRC) cell lines revealed that FBN2 and TCERG1L gene silencing is associated with DNA hypermethylation of a CpG island in the promoter region. In this study, promoter DNA hypermethylation of FBN2 and TCERG1L in CRC occurs as an early and cancer-specific event in colorectal cancer. Both genes showed high frequency of methylation in colon cancer cell lines (>80% for both of genes), adenomas (77% for FBN2, 90% for TCERG1L, n=39), and carcinomas (86% for FBN2, 99% for TCERG1L, n=124). Bisulfite sequencing confirmed cancer-specific methylation of FBN2 and TCERG1L of promoters in colon cancer cell line and cancers but not in normal colon. Methylation of FBN2 and TCERG1L is accompanied by downregulation in cell lines and in primary tumors as described in the Oncomine™ website. Together, our results suggest that gene silencing of FBN2 and TCERG1L is associated with promoter DNA hypermethylation in CRC tumors and may be excellent biomarkers for the early detection of CRC.
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