Aberrant DNA methylation occurs in colon neoplasms arising in the azoxymethane colon cancer model.
Aberrant DNA methylation occurs in colon neoplasms arising in the azoxymethane colon cancer model.
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DOI：
10.1002/mc.20581
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发表时间：
2010-01
影响因子：
4.6
通讯作者：
Grady, William M.
中科院分区：
文献类型：
--
作者：
Borinstein, Scott C.;Conerly, Melissa;Dzieciatkowski, Slavomir;Biswas, Swati;Washington, M. Kay;Trobridge, Patty;Henikoff, Steve;Grady, William M.
小鼠肠道肿瘤模型提高了我们对基因突变在结直肠恶性肿瘤中的作用的理解。然而，这些系统在研究表观遗传改变在肠道肿瘤中的作用方面的效用仍有待确定。因此，我们评估了异常DNA甲基化在偶氮甲烷（AOM）结肠癌啮齿动物模型中的作用。AOM诱导的肿瘤显示整体DNA低甲基化，这与人类结直肠癌相似。接下来，我们评估了一组候选基因的甲基化状态，这些基因先前在人类癌症或小鼠恶性肿瘤模型中被证明是异常甲基化的。这一分析揭示了不同的DNA甲基化模式是基因特异性的。Zik1和Gja9表现出癌症特异性的异常DNA甲基化，而Cdkn2a/p16、Igfbp3、Mgmt、Id4和Cxcr4在AOM肿瘤和正常结肠粘膜中均出现甲基化。肿瘤中未检测到Dapk1或Mlt1的异常甲基化，但正常结肠粘膜样本显示这些基因的甲基化。最后，p19Arf、Tslc1、Hltf和Mlh1在AOM肿瘤和正常结肠粘膜中均未甲基化。因此，异常DNA甲基化确实发生在AOM肿瘤中，尽管异常甲基化基因的频率似乎不如人类结直肠癌常见。需要进一步的研究来进一步表征AOM肿瘤中异常甲基化基因的模式。
Mouse models of intestinal tumors have advanced our understanding of the role of gene mutations in colorectal malignancy. However, the utility of these systems for studying the role of epigenetic alterations in intestinal neoplasms remains to be defined. Consequently, we assessed the role of aberrant DNA methylation in the azoxymethane (AOM) rodent model of colon cancer. AOM induced tumors display global DNA hypomethylation, which is similar to human colorectal cancer. We next assessed the methylation status of a panel of candidate genes previously shown to be aberrantly methylated in human cancer or in mouse models of malignant neoplasms. This analysis revealed different patterns of DNA methylation that were gene specific. Zik1 and Gja9 demonstrated cancer-specific aberrant DNA methylation, whereas, Cdkn2a/p16, Igfbp3, Mgmt, Id4, and Cxcr4 were methylated in both the AOM tumors and normal colon mucosa. No aberrant methylation of Dapk1 or Mlt1 was detected in the neoplasms, but normal colon mucosa samples displayed methylation of these genes. Finally, p19Arf, Tslc1, Hltf, and Mlh1 were unmethylated in both the AOM tumors and normal colon mucosa. Thus, aberrant DNA methylation does occur in AOM tumors, although the frequency of aberrantly methylated genes appears to be less common than in human colorectal cancer. Additional studies are necessary to further characterize the patterns of aberrantly methylated genes in AOM tumors.
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影响因子：
56.9
作者：
Gaudet, F;Hodgson, JG;Jaenisch, R
通讯作者：
Jaenisch, R
影响因子：
11.2
作者：
Hahn MA;Hahn T;Lee DH;Esworthy RS;Kim BW;Riggs AD;Chu FF;Pfeifer GP
通讯作者：
Pfeifer GP
影响因子：
4.8
作者：
Denisenko, ON;ONeill, B;Bomsztyk, K
通讯作者：
Bomsztyk, K
影响因子：
4.2
作者：
Cummings, Damian M.;Yamazaki, Irene;Levine, Michael S.
通讯作者：
Levine, Michael S.
影响因子：
7.3
作者：
Ferracin, M.;Gafa, R.;Negrin, M.
通讯作者：
Negrin, M.