The overall goal of the current proposal is to understand, further, the role of altered regulation and patterns of DNA methylation in the progression of colon cancer. The investigators have described incremental increases in activity of the enzyme, DNA methyltransferase (DNA-MTase), from the earliest to the latest progression stage of colon neoplasia. In this setting they have also defined, for multiple genes important to the tumorigenic process, hypermethylation of promoter region CpG islands associated with loss of gene transcription. Both events, increased DNA- MTase and hypermethylation of selected genes, also increase in colon mucosa as a function of age. The current studies seek to determine, further, how, in colon mucosa, the above alterations in DNA methylation regulation and patterns may be linked to one another during aging and in predisposition states for colon tumors. The cell types responsible for these events during tumor progression will be elucidated. A colon tumor progression model for gene hypermethylation events will be constructed. For specific genes, the role of inactivation in colon tumorigenesis will be assessed. Finally, the investigators seek to determine whether increases or decreases in DNA-MTase activity directly influence the rate, and extent, of colon tumor progression and whether this enzyme may constitute a legitimate target for colon cancer prevention and early intervention strategies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA054396-10
Application #
6172100
Study Section
Pathology B Study Section (PTHB)
Program Officer
Lively, Tracy (LUGO)
Project Start
1991-04-01
Project End
2002-03-31
Budget Start
2000-04-01
Budget End
2002-03-31
Support Year
10
Fiscal Year
2000
Total Cost
$362,833
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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