Induction of Tumors in Mice by Genomic Hypomethylation
Max Delbrück Center · Whitehead Institute for Biomedical Research · +3 more institutions
Abstract
Genome-wide DNA hypomethylation occurs in many human cancers, but whether this epigenetic change is a cause or consequence of tumorigenesis has been unclear. To explore this phenomenon, we generated mice carrying a hypomorphic DNA methyltransferase 1 (Dnmt1) allele, which reduces Dnmt1 expression to 10% of wild-type levels and results in substantial genome-wide hypomethylation in all tissues. The mutant mice were runted at birth, and at 4 to 8 months of age they developed aggressive T cell lymphomas that displayed a high frequency of chromosome 15 trisomy. These results indicate that DNA hypomethylation plays a causal role in tumor formation, possibly by promoting chromosomal instability.
Citation impact
- FWCI
- 34.59
- Percentile
- 100%
- References
- 34
Authors
8- FGFrançois GaudetCorresponding
Max Delbrück Center, Whitehead Institute for Biomedical Research, UCSF Helen Diller Family Comprehensive Cancer Center, Massachusetts Institute of Technology, Ludwig-Maximilians-Universität München
- JHJohn Hodgson
Max Delbrück Center, Whitehead Institute for Biomedical Research, UCSF Helen Diller Family Comprehensive Cancer Center, Massachusetts Institute of Technology, Ludwig-Maximilians-Universität München
- AEAmir Eden
Max Delbrück Center, Whitehead Institute for Biomedical Research, UCSF Helen Diller Family Comprehensive Cancer Center, Massachusetts Institute of Technology, Ludwig-Maximilians-Universität München
- LJLaurie Jackson‐Grusby
Max Delbrück Center, Whitehead Institute for Biomedical Research, UCSF Helen Diller Family Comprehensive Cancer Center, Massachusetts Institute of Technology, Ludwig-Maximilians-Universität München
- JDJessica Dausman
Max Delbrück Center, Whitehead Institute for Biomedical Research, UCSF Helen Diller Family Comprehensive Cancer Center, Massachusetts Institute of Technology, Ludwig-Maximilians-Universität München
Topics & keywords
- Biology
- Computational biology
- Genetics
- Cancer research
- Good health and well-being