CpG island methylation in familial colorectal cancer patients not fulfilling the Amsterdam criteria.

CpG island methylation in familial colorectal cancer patients not fulfilling the Amsterdam criteria.
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DOI:
10.3346/jkms.2008.23.2.270
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发表时间:
2008-04
影响因子:
4.5
通讯作者:
Kim JC
Kim JC
中科院分区:
医学4区
文献类型:
--
作者:
Kim HC;Lee HJ;Roh SA;Kim JS;Yu CS;Kim JC

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为了确定甲基化在有家族史的结直肠癌患者中的作用,我们招募了25名有结直肠癌家族史但没有hMLH1和hMSH2基因突变的结直肠癌患者。30例散发性结直肠癌患者作为对照。采用甲基化特异性PCR检测正常黏膜和肿瘤组织中COX2、MGMT、hMLH1、TIMP3、p16和MINT2的甲基化状态。在有家族史的患者中,TIMP3的甲基化频率从4.0%到44.4%不等,而在散发性结直肠癌患者中,TIMP3的甲基化频率从6.7%到p16的50.0%不等。25例家族史患者中有9例(36.0%)为甲基化易感性,30例散发性癌症患者中有9例(30.0%)为甲基化易感性,其甲基化指数分别为0.19和0.16 (p=0.522)。个体基因方面,有家族病史的结直肠癌患者MGMT甲基化率较高(44.0%比13.0%,p=0.016),散发性结直肠癌患者p16甲基化率较高(50.0%比8.7%,p=0.046)。虽然肿瘤抑制基因的CpG岛甲基化可能在结直肠癌发生中发挥作用,但涉及的基因在有和没有结直肠癌家族史的患者的肿瘤中可能是不同的。
To determine the role of methylation in colorectal cancer patients with a family history, we enrolled 25 colorectal cancer patients with a family history of colorectal cancer but without a mutation in the hMLH1 and hMSH2 genes. Thirty patients with sporadic colorectal cancer were included as control. The methylation status of COX2, MGMT, hMLH1, TIMP3, p16, and MINT2 in normal mucosa and tumor were assessed using methylation-specific PCR. In patients with a family history, the methylation frequency ranged from 4.0% for TIMP3 to 44.4% for MGMT, whereas, in patients with sporadic colorectal cancer, it ranged from 6.7% for TIMP3 to 50.0% for p16. Nine of the 25 patients with family history (36.0%) were classified as methylation-prone, and nine of the 30 patients with sporadic cancers (30.0%) were as methylation-prone, making their methylation indices 0.19 and 0.16, respectively (p=0.522). As for the individual genes, the methylation rate of MGMT was higher in colorectal cancer patients with family history (44.0% vs. 13.0%, p=0.016), whereas the methylation rate of p16 was higher in sporadic colorectal cancers (50.0% vs. 8.7%, p=0.046). While CpG island methylation of tumor suppressor genes may play a role in colorectal carcinogenesis, the genes involved may be different between tumors of patients with and without a family history of colorectal cancer.
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