肿瘤的干细胞来源学说获得新支持

yujian623

最近，来自USC的研究人员最近在解决一个争论了十多年的问题上取得了重大进展。这个争论的中心是：干细胞在肿瘤的发展中扮演的角色。根据此项研究发现（即将在Nature Genetics发表，现在可以在线获得），在肿瘤中始终保持静止的基因中，那些在胚胎干细胞被逆向抑制的基因过度表达。这个联系增加了对讨论越来越多的肿瘤来自小部分干细胞理论的支持。
  USC在观察了177个由PcG组蛋白抑制的基因，77个完全说明与肿瘤相关DNA修饰酶的证据（称之为甲基化）。研究人员发现，一些在胚胎干细胞中受Polycomb抑制的基因实质上被DNA甲基化提前标记为永久静止。阻止胚胎干细胞分化，那样，在生命晚期，它们就可以成为肿瘤发展的基础。USC的研究者作了与乳腺癌、结肠癌、肺癌和卵巢癌有关的观察。
USC的研究不仅为肿瘤干细胞起源学说提供了实验证据，而且也支持了肿瘤中在很早期就包含了胚胎变化的说法。研究者发现肿瘤出现在已经发生胚胎学变化的细胞中，这指出了在肿瘤发展中，实验胚胎事件在遗传事件发生之前进行。这一个相对较新的理论正在得到科学家们的支持。     

这一研究显示肿瘤起源于干细胞，，这对于监督胚胎畸变非常重要，可以防止干细胞移植应用中，人们接受有潜在致癌倾向的细胞。下一步研究人员将集中研究是什么引起一些基因从短期抑制转变成永久静止的。



Figure 1. PRC2 promoter occupancy in human ES cells and DNA methylation in human colorectal tumors and matched normal mucosa.



(a) SUZ12 and EED occupancy data and H3K27 trimethylation status for 177 genes were obtained from ref. 7 and are indicated by blue bars. Gene identities and primer and probe sequences are supplied in the Supplementary Note. DNA methylation data were obtained from ref. 8. PMR values are indicated by colored bars as shown in the key at the bottom of a. Genes are ranked by decreasing cancer-specific DNA methylation as defined by the differential mean PMR between tumor and normal samples. The 77 genes with a differential mean PMR 2 are grouped in the top part of the panel, and the 100 genes with a differential <2 are represented in the lower part of the panel. (b) A model for the progression of epigenetic marks from reversible repression in ES cells to aberrant DNA methylation in cancer precursor cells and persistent gene silencing in cancer cells.




原文出处：

Nature Genetics  January 2007, Volume 39 No 1

Epigenetic stem cell signature in cancer
Martin Widschwendter, Heidi Fiegl, Daniel Egle, Elisabeth Mueller-Holzner, Gilbert Spizzo, Christian Marth, Daniel J Weisenberger, Mihaela Campan, Joanne Young, Ian Jacobs & Peter W Laird
Published online: 31 December 2006 | doi:10.1038/ng1941
Abstract | Full text | PDF (207K) | Supplementary Information