文章：

癌症中的表观遗传基因沉默-早期致癌通路成瘾的机制？

Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction?

原文发布日期：2006-02-01

DOI: 10.1038/nrc1799

类型: Review Article

开放获取: 否

要点：

1. Epigenetic gene silencing, which is associated with aberrant methylation of promoter DNA and transcriptional repression, is an important mechanism for the loss of gene function in cancer.
2. Silencing can occur during the early stages of human tumour progression — in pre-invasive lesions — and involves disruption or over-activation of key developmental pathways and cell-signalling properties.
3. These early gene-silencing events might be crucial for inducing the aberrant, early, clonal expansion of cells through the above alterations in key cell pathways.
4. Early gene-silencing events might 'addict' cells to certain oncogenic pathways. This 'epigenetic addiction' could predispose cells to the accumulation of genetic mutations in these same pathways, which drives tumour progression.

要点翻译：

1. 表观遗传基因沉默与启动子DNA异常甲基化和转录抑制相关，是癌症中基因功能丧失的重要机制。
2. 沉默可发生于人类肿瘤进展的早期阶段——即浸润前病变期——涉及关键发育通路和细胞信号特性的破坏或过度激活。
3. 这些早期基因沉默事件可能通过改变关键细胞通路，对诱导细胞异常早期克隆扩增起关键作用。
4. 早期基因沉默事件可能使细胞"成瘾"于某些致癌通路。这种"表观遗传成瘾"可能使细胞易于在这些相同通路中积累基因突变，从而驱动肿瘤进展。

英文摘要：

Chromatin alterations have been associated with all stages of tumour formation and progression. The best characterized are epigenetically mediated transcriptional-silencing events that are associated with increases in DNA methylation — particularly at promoter regions of genes that regulate important cell functions. Recent evidence indicates that epigenetic changes might 'addict' cancer cells to altered signal-transduction pathways during the early stages of tumour development. Dependence on these pathways for cell proliferation or survival allows them to acquire genetic mutations in the same pathways, providing the cell with selective advantages that promote tumour progression. Strategies to reverse epigenetic gene silencing might therefore be useful in cancer prevention and therapy.

摘要翻译： 

染色质改变与肿瘤形成和进展的所有阶段相关。研究最深入的是由表观遗传介导的转录沉默事件，这些事件与DNA甲基化水平升高有关，尤其是在调控重要细胞功能的基因启动子区域。最新证据表明，在肿瘤发展的早期阶段，表观遗传变化可能使癌细胞“依赖”于改变的信号转导通路。这些通路对细胞增殖或生存的依赖使细胞能够在同一通路中获得基因突变，从而为细胞提供选择性优势，促进肿瘤进展。因此，逆转表观遗传基因沉默的策略可能有助于癌症的预防和治疗。

原文链接：

Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction?