Loss of imprinting of IGF2 as an epigenetic marker for the risk of human cancer.
Loss of imprinting of IGF2 as an epigenetic marker for the risk of human cancer.
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DOI：
10.1155/2007/363464
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Cui H
中科院分区：
文献类型：
--
作者：
Cui H
IGF2是第一个被发现在人类和小鼠中只从父系等位基因中印记和表达的基因。IGF2也是第一个在人类癌症中表现出印记丢失（LOI）或异常印记的印记基因。显然，LOI或IGF 2的母体等位基因的再激活与IGF 2表达的增加相关，其随后可能在人类癌症的发病中起重要作用。最重要的发现是IGF2的LOI与发展人类结直肠癌的风险之间的关联。LOI不仅发生在结肠癌组织中，而且也发生在匹配的正常组织和外周血细胞中。初步研究表明IGF2的LOI与结直肠癌家族史以及个人史之间存在显著相关性，提示IGF2的LOI可能是预测个体患结肠癌风险的有价值的生物分子标志物。最近的表观遗传祖细胞模型表明，人类癌症可能有一个共同的基础，涉及由“肿瘤祖基因”介导的祖细胞的表观遗传破坏，并提出非肿瘤性但表观遗传破坏的祖细胞可能是癌症风险评估和预防的重要目标。
IGF2 is the first gene discovered to be imprinted and expressed exclusively from the paternal allele in both human and mouse. IGF2 is also the first imprinted gene displaying loss of imprinting (LOI) or aberrant imprinting in human cancers. Evidently, LOI or reactivation of the maternal allele of IGF2 is associated with an increase of IGF2 expression that may subsequently play an important role in the onset of human cancers. The most important discovery was the association of LOI of IGF2 with the risk of developing human colorectal cancer. LOI occurs not only in colon cancer tissues, but also in matched normal tissues and peripheral blood cells. A pilot study indicated a significant relationship between LOI of IGF2 and family history as well as personal history of colorectal cancer, suggesting that LOI of IGF2 might be a valuable biomolecular marker of predicting an individual's risk for colon cancer. A recent epigenetic progenitor model suggested that human cancers might have a common basis that involves an epigenetic disruption of progenitor cells mediated by “tumor progenitor genes” and proposed that non-neoplastic but epigenetically disrupted progenitor cells might be an important target for cancer risk assessment and prevention.
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