Induction of Tumors in Mice by Genomic Hypomethylation
SciencePublished 17 April 2003
François Gaudet, John Hodgson, Amir Eden, Laurie Jackson‐Grusby, Jessica Dausman, Joe W. Gray
Citations1,487
SJR quartileQ1
SJR score10.42
SNIP6.62
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TL;DR
Results indicate that DNA hypomethylation plays a causal role in tumor formation, possibly by promoting chromosomal instability.
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.
Keywords
Biochemistry, Genetics and Molecular Biology
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