Epigenetic response of imprinted domains during carcinogenesis.
Epigenetic response of imprinted domains during carcinogenesis.
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癌变期间印迹域的表观遗传反应。
DOI：
10.1186/s13148-017-0393-8
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发表时间：
2017
影响因子：
5.7
通讯作者：
Kim J
中科院分区：
文献类型：
--
作者：
Bretz CL;Langohr IM;Kim J
印迹结构域已被确定为癌发生过程中异常DNA甲基化的靶点，但尚不清楚这些表观遗传学改变何时发生以及它们如何促进肿瘤进展。印迹结构域中关键顺式调控元件的表观遗传不稳定性可以同时激活原癌基因和关闭肿瘤抑制基因。因此，为了进一步表征致癌过程中印迹结构域的表观遗传反应，我们比较了KrasG 12 D突变诱导的两种根本不同的小鼠肿瘤（良性和恶性）中印迹结构域内各种顺式调控元件的DNA甲基化的稳定性。我们报告说，印迹域保持稳定的良性过程中，但高度敏感的表观遗传学改变浸润性病变。在良性肿瘤的整个过程中，DNA甲基化在印迹结构域中的保留表明印迹基因不参与致癌作用的启动或肿瘤的生长。然而，在浸润性病变的印记控制区域的DNA甲基化变化的频繁检测表明，印记基因与肿瘤细胞获得的能力，挑战组织边界。总的来说，这项研究表明，当良性肿瘤细胞转化为恶性肿瘤时，印迹结构域是DNA超甲基化的目标。因此，监测印迹结构域内的DNA甲基化可能有助于评估肿瘤的进展。本文的在线版本（doi：10.1186/s13148-017-0393-8）包含补充材料，可供授权用户使用。
Imprinted domains have been identified as targets for aberrant DNA methylation during carcinogenesis, but it remains unclear when these epigenetic alterations occur and how they contribute to tumor progression. Epigenetic instability at key cis-regulatory elements within imprinted domains can concomitantly activate proto-oncogenes and turn off tumor suppressor genes. Thus, to further characterize the epigenetic response of imprinted domains during carcinogenesis, we compared the stability of DNA methylation at a variety of cis-regulatory elements within imprinted domains in two fundamentally different mouse tumors, benign and malignant, induced by the KrasG12D mutation. We report that imprinted domains remain stable in benign processes but are highly susceptible to epigenetic alterations in infiltrative lesions. The preservation of DNA methylation within imprinted domains in benign tumors throughout their duration suggests that imprinted genes are not involved with the initiation of carcinogenesis or the growth of tumors. However, the frequent detection of DNA methylation changes at imprinting control regions in infiltrative lesions suggest that imprinted genes are associated with tumor cells gaining the ability to defy tissue boundaries. Overall, this study demonstrates that imprinted domains are targeted for DNA hypermethylation when benign tumor cells transition to malignant. Thus, monitoring DNA methylation within imprinted domains may be useful in evaluating the progression of neoplasms. The online version of this article (doi:10.1186/s13148-017-0393-8) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Bretz, Corey L.;Langohr, Ingeborg M.;Kim, Joomyeong
通讯作者：
Kim, Joomyeong
影响因子：
3.5
作者：
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7.2
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Bartolomei, Marisa S.
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56.9
作者：
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通讯作者：
Dulac, Catherine
影响因子：
7.2
作者：
Bartolomei, Marisa S;Ferguson-Smith, Anne C
通讯作者：
Ferguson-Smith, Anne C