The current grant focuses upon studies of aberrant DNA methylation patterns in human cancer cells. Specifically, we are exploring the causes and consequences of regional increases in DNA methylation in transformed cells. These changes may mark and/or contribute to the chromosome structural alterations underlying abnormal gene expression events important for the initiation and/or progression of human tumors. The short arm of chromosome 11 appears to be a """"""""hot spot"""""""" for DNA hypermethylation which could contribute to loss of gene expression. Current studies are examining whether such changes also exist in other genomic areas specifically involved in the pathogenesis of individual human cancers. Temperature sensitive viruses are being used to delineate the precise timing of the increased methylation following cell transformation. Gene insertion studies will be used to examine transformation effects upon specific regions of DNA. Finally, a model for increased cellular DNA methylating capacity has been constructed to study the resultant molecular changes and the phenotypic consequences for eukaryotic cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA043318-07
Application #
3185510
Study Section
Pathology B Study Section (PTHB)
Project Start
1986-09-30
Project End
1994-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
7
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Vaz, Michelle; Hwang, Stephen Y; Kagiampakis, Ioannis et al. (2017) Chronic Cigarette Smoke-Induced Epigenomic Changes Precede Sensitization of Bronchial Epithelial Cells to Single-Step Transformation by KRAS Mutations. Cancer Cell 32:360-376.e6
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Azad, Nilofer; Zahnow, Cynthia A; Rudin, Charles M et al. (2013) The future of epigenetic therapy in solid tumours--lessons from the past. Nat Rev Clin Oncol 10:256-66

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