Mouse embryos cloned from brain tumors.
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 postimplantation embryos with typical cell layers. Thus, tumor cells can be epigenetically reprogrammed into normal cell types. This approach could lead to a general strategy for assessing genetic and epigenetic contributions to tumorigenesis.
Li
Leyi
L
Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Connelly
Michele C
MC
Wetmore
Cynthia
C
Curran
Tom
T
Morgan
James I
JI
D000818:Animals; D001755:Blastocyst / Q000502:physiology*; D001757:Blastomeres / Q000502:physiology*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000648:ultrastructure; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005260:Female; D008527:Medulloblastoma / Q000235:genetics* / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D053652:Nuclear Transfer Techniques; D016133:Polymerase Chain Reaction