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. Our analyses have identified a premalignant expression signature that 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 refined evidence for antagonistic action of DNA methylation and binding of the nuclear at genomic loci. Using a quantitative DNA methylation assay (epitapher) and licrodissection, we profiled several gene loci that are part of the premalignant signature ovarian cancer cell lines. While the majority of loci did not reveal any difference between BRCA1 cancers and normal risk fallopian tube epithelia, a small fraction of cancers indicate increased methylation of the CDKN1C tumor suppressor gene. Contrary toto published reports, our data exclude a role for LOH or estrogen-inducible antisense RNAs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2011
- Accession Number
- ADA564165
Entities
People
- Anton Krumm
Organizations
- University of Washington