Premalignant Genetic and Epigenetic Alterations in Tubal Epithelium from Women with BRCA1 Mutations
Abstract
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. DNA methylation analysis of isolated and pooled samples by laser-capture microscopy indicates that increased cytosine methylation at the CDKN1C gene may contribute to epigenetic changes that mark ovarian cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 14, 2010
- Accession Number
- ADA541654
Entities
People
- Anton Krumm
Organizations
- University of Washington