Get started
Work

Reprogramming of a melanoma genome by nuclear transplantation

Year: 2004
Type: preprint
Abstract: We have used nuclear transplantation to test whether the reprogramming activity of oocytes can reestablish developmental pluripotency of malignant cancer cells. We show here that the nuclei of leukemia, lymphoma, and breast cancer cells could support normal preimplantation development to the blastocyst stage but failed to produce embryonic stem (ES) cells. However, a blastocyst cloned from a RAS-inducible melanoma nucleus gave rise to ES cells with the potential to differentiate into multiple cell types in vivo including melanocytes, lymphocytes, and fibroblasts. Chimeras produced from these ES cells developed cancer with higher penetrance, shorter latency, and an expanded tumor spectrum when compared with the donor mouse model. These results demonstrate that the secondary changes of a melanoma nucleus are compatible with a broad developmental potential but predispose mice to melanomas and other malignant tumors on reactivation of RAS. Our findings serve as a paradigm for studying the tumorigenic effect of a given cancer genome in the context of a whole animal.
DOI: 10.1101/gad.1213504
Authors: Konrad Hochedlinger, Robert Blelloch, Cameron Brennan, Yasuhiro Yamada, Minjung Kim, Lynda Chin, Rudolf Jaenisch
Institutions: Brigham and Women's Hospital, Harvard University, Dana-Farber Cancer Institute, Dana-Farber/Harvard Cancer Center, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Dana-Farber Brigham Cancer Center
Language: English
Open Access status: green
Awards: G2541361104, GENETIC DISEASE, CANCER, AND MAMMALIAN DEVELOPMENT, Pathobiology of Cancer at the Host and Population Level, The genetic Basis of Melanoma Metastasis, G572791594, GENOMIC IMPRINTING AND THE CLONING OF MICE
OpenAlex ID: W2153199196
Cites: 53
Cited by: 377
Related to: 10