TY - JOUR
T1 - Induction of tumors in mice by genomic hypomethylation
AU - Gaudet, François
AU - Hodgson, J. Graeme
AU - Eden, Amir
AU - Jackson-Grusby, Laurie
AU - Dausman, Jessica
AU - Gray, Joe W.
AU - Leonhardt, Heinrich
AU - Jaenisch, Rudolf
PY - 2003/4/18
Y1 - 2003/4/18
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1083558
DO - 10.1126/science.1083558
M3 - Article
C2 - 12702876
AN - SCOPUS:0242584449
SN - 0036-8075
VL - 300
SP - 489
EP - 492
JO - Science
JF - Science
IS - 5618
ER -