“Mouse Embryos Cloned from Brain Tumors”, 2003-06 (; similar):
Cancer cells escape from growth control by accumulating genetic and epigenetic alterations. In rare instances, epigenetic changes alone are oncogenic. Furthermore, agents that modify DNA methylation or chromatin structure can restore a normal phenotype to cells harboring oncogenic mutations. However, it is unclear to what extent epigenetic reprogramming can reverse oncogenesis.
Using somatic nuclear transfer, we show that medulloblastomas arising in Ptc1± mice can direct preimplantation development. Additionally, blastocysts derived from medulloblastoma nuclei form post-implantation embryos with typical cell layers. Thus, tumor cells can be epigenetic ally reprogrammed into normal cell types.
This approach could lead to a general strategy for assessing genetic and epigenetic contributions to tumorigenesis.
…Cancers arise through the accumulation of genetic mutations1 and epigenetic modifications2, 3. Although many proto-oncogenes and tumor suppressor genes are widely expressed, the mutation of these genes is associated with cancer of specific organs or cell types4, 5. This suggests that, to some extent, malignant growth depends on epigenetic factors that are governed by the cellular context in which a tumor arises. Teratocarcinomas can arise through purely epigenetic changes and represent an extreme case in which the transformed phenotype can be abrogated under appropriate conditions6, 7, 8. Indeed, in early chimera studies, it was demonstrated that teratocarcinoma cells are able to contribute to the germ line, ultimately giving rise to adult mice6. In a frog renal carcinoma model, the transfer of nuclei from tumor cells into oocytes was reported to reverse oncogenesis and to direct development to the tadpole stage9. Although this was suggested to occur through epigenetic reprogramming, subsequently it was found that the transforming gene, which was encoded by a Herpesvirus episome10, was lost during the nuclear transfer procedure11. Here, we investigate the possibility of whether a tumor cell nucleus, in which transformation is caused by somatic mutation, can be epigenetically reprogrammed into normal tissues.
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