Gene Set: KINNEY_DNMT1_METHYLATION_TARGETS

Standard name KINNEY_DNMT1_METHYLATION_TARGETS
Systematic name M2508
Brief description Hypomethylated genes in prostate tissue from mice carrying hypomorphic alleles of DNMT1 [GeneID=1786].
Full description or abstract Previous studies have shown that tumor progression in the transgenic adenocarcinoma of mouse prostate (TRAMP) model is characterized by global DNA hypomethylation initiated during early-stage disease and locus-specific DNA hypermethylation occurring predominantly in late-stage disease. Here, we utilized Dnmt1 hypomorphic alleles to examine the role of Dnmt1 in normal prostate development and in prostate cancer in TRAMP. Prostate tissue morphology and differentiation status was normal in Dnmt1 hypomorphic mice, despite global DNA hypomethylation. TRAMP; Dnmt1 hypomorphic mice also displayed global DNA hypomethylation, but were characterized by altered tumor phenotype. Specifically, TRAMP; Dnmt1 hypomorphic mice exhibited slightly increased tumor incidence and significantly increased pathological progression at early ages and, conversely, displayed slightly decreased tumor incidence and significantly decreased pathological progression at advanced ages. Remarkably, hypomorphic Dnmt1 expression abrogated local and distant site macrometastases. Thus, Dnmt1 has tumor suppressor activity in early-stage prostate cancer, and oncogenic activity in late stage prostate cancer and metastasis. Consistent with the biological phenotype, epigenomic studies revealed that TRAMP; Dnmt1 hypomorphic mice show dramatically reduced CpG island and promoter DNA hypermethylation in late-stage primary tumors compared to control mice. Taken together, the data reveal a crucial role for Dnmt1 in prostate cancer and suggest that Dnmt1-targeted interventions may have utility specifically for advanced and/or metastatic prostate cancer.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 20584988   Authors: Kinney SR,Moser MT,Pascual M,Greally JM,Foster BA,Karpf AR
Exact source Table 2
Related gene sets (show 16 gene sets from the same authors)
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Organism Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
Source platform Mouse_RefSeq
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Version history 3.1: First introduced

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