Premalignant Genetic and Epigenetic Alterations in Tubal Epithelium from Women with BRCA1 Mutations
Annual rept. 15 Sep 2008-14 Sep 2009
SEATTLE UNIV WA
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Increasing evidence suggests that many types of ovarian cancers originate within the fallopian tube. The scope of this Translational Partnership project is to define a unique premalignant gene expression profile and to identify causal epigenetic relationships. As outlined in the statement of work, our analyses have identified a premalignant expression signature which potentially reflects early steps in ovarian carcinogenesis. While genes differentially expressed in BRCA1 normal Fallopian Tube epithelia and BRCA1 ovarian carcinoma were investigated in the Swisher lab, we have further established the proof-of-principle that demonstrates the role of DNA methylation of CTCF binding sites in cancer tissues. We gathered evidence that genes that are part of the premalignant signature are differentially methylated in ovarian cancer cell lines. We have begun to isolate and pool samples by laser-capture microscopy. In the coming year, we will perform extensive mapping of DNA methylation to precisely determine epigenetic changes that affect the normal expression of genes in ovarian cancer.
- Anatomy and Physiology
- Medicine and Medical Research