2003 Liz Tilberis Grant Recipient – Susan K. Murphy
Susan K. Murphy, Ph.D.
Duke University Medical Center
How Chemical Alterations to the DNA– but not its Sequence– May Play a Role in Ovarian Cancer
The molecular mechanisms involved in the development of ovarian cancer are poorly understood. But it is possible that epigenetic mutations, chemical alterations to the DNA that do not change the sequence or the genetic code of DNA, may be partially responsible. These chemical changes, such as the addition of a methyl group to DNA, may affect the ability of a gene to normally do its job. In cancer cells, inappropriate epigenetic changes can result in uncontrolled cell growth by shutting down genes for growth inhibitors and/or turning on growth stimulator genes.
Certain genes we inherit from our parents have epigenetic changes and are called imprinted genes. Imprinted genes are typically involved in regulating growth and the maternal and paternal copies normally exhibit opposite patterns of DNA methylation. This epigenetic parental distinction enables imprinted genes to always be expressed from only one of the two chromosomes inherited from either of one’s parents. The PEG3 (Paternally Expressed Gene 3) and the IGF2 (insulin-like Growth Factor 2) are two imprinted genes and exhibit abnormal expression in ovarian cancer. An important objective of this research is to determine whether the expression of these genes in ovarian cancer can be attributed to changes in the methylation patterns.
Studies have shown that in colon cancer, abnormal methylation of IGF2 is present in the surrounding normal colonic tissue and in the white blood cells of many colon cancer patients. These findings suggest that some people are susceptible to cancer because they do not maintain proper methylation of imprinted genes in their normal tissues. Therefore, methylation defects in the imprinted genes proposed for study in ovarian cancer will also be assessed for their methylation status in white blood cells to determine if such a test will allow for identification of individuals at high risk of developing ovarian and other cancers.
The five-year survival rate for ovarian cancer has increased by only 8% in the last 30 years.
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