The Use of a New Technique to Study DNA Methylation in Breast Cancer
Annual rept. 1 Oct 1998-30 Sep 1999
NORTH SHORE HOSPITAL MANHASSET NY
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The mechanisms of breast cancer development are incompletely understood. A reasonable hypothesis is that the evolution of this disease is caused by various genetic, and non-genetic factors. These may occur in multiple steps which eventually precipitate genetic lesions such as mutations, or deletions. One causative factor may be imbalanced DNA methylation. A new technique, Methylation Differential Display MDD, has been developed to explore DNA methylation patterns in breast cancer. BR5O was one of the hypomethylated DNA fragments isolated by MDD. Further study of BR5O has led to the discovery of a novel gene, TSP5O. The TSP5O gene product is homolog to several human serine proteases which indicates that it may encode a serine protease like protein. Northern analysis of sixteen different types of normal human tissues suggest that TSP5O was highly, and specifically expressed in human testes, which indicates that it might possess a unique biological functions in that organ. Methylation status analysis in normal human testes and other tissues showed a correlation between DNA methylation and gene expression. Most importantly, RT-PCR analysis of eighteen paired breast cancer tissues found that, in 28 of the cancer samples, the TSP5O gene was differentially expressed.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research