Mammary Cancer and Activation of Transposable Elements

Abstract

The purpose of this project is to investigate molecular events occurring in the preclinical stages of mammary cancer. Specifically, the project investigates the intersection between the development of genome demethylation, retrotransposon transcriptional activity, and retrotransposon-driven transcription of cellular genes in an engineered mouse model of mammary cancer. RNA-seq and Methyl-MAPS methylation analysis was performed on uni-parous and tri-parous tumor-prone and control mice. We discovered genome-wide demethylation that occurs in tumor-prone tri-parous mice, that differs substantially from the long-hypomethylated domains that characterize breast tumors. We thus propose that the wide-spread remodeling of DNA methylation patterns found in tumors may begin at this early pre-clinical stages modeled in this study. However, these changes do not appear to impact transcription at this stage. During this project we have developed powerful computational tools for elucidating relationships between DNA methylation and expression. These tools have broad potential to affect our understanding of the functions of DNA methylation in breast cancer and may impact cancer prevention in the future.

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Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2015
Accession Number
ADA618871

Entities

People

  • John R. Edwards

Organizations

  • Washington University in St. Louis

Tags

DTIC Thesaurus Topics

  • Algorithms
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cells
  • Colon Cancer
  • Data Sets
  • Gene Expression
  • Genetics
  • High Resolution
  • Machine Learning
  • Materials
  • Methylation
  • Neoplasms
  • Nucleic Acids
  • Stem Cells
  • Supervised Machine Learning

Fields of Study

  • Biology

Readers

  • Molecular and genetic basis of cancer.