Characterization of Early Genomic Changes in Mammary Glande of High Risk Women

Abstract

The purpose of this project was to address the critical question of identifying early genomic changes that occur in the mammary glands of patients with increased predisposition to breast cancer due to germ-line mutations in BRCAl/2 genes. Identification of these early changes will improve our understanding of the mechanisms of tumorigenensis in these high-risk patients and therefore should aid in devising early detection, diagnosis, and prevention strategies for such women at risk. Over the course of the project, we tested the hypothesis that genomic changes may be detected, not only in histologically abnormal and malignant breast tissues, but also in morphologically normal tissues as well as in areas with pathologically benign changes. We have clearly shown that genetic changes in areas with pathologically benign changes. We have clearly shown that genetic changes in the form of LOH are present in the non-malignant breast tissues in addition to the tumor, suggesting that these non-malignant tissues already harbor significant genetic alterations that may predispose them to malignant transformation. Our results support the hypothesis that there is a "field effect" of early genetic events preceding morphologic changes in the mammary glands of BRCA mutation carriers. To follow up on these findings we have recently initiated a study aiming at developing and testing molecular markers for early detection and diagnosis of hereditary breast cancer in BRCAl/2 carriers.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2003
Accession Number
ADA420119

Entities

People

  • Bassem R. Haddad

Organizations

  • Georgetown University

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cancer
  • Carcinoma
  • Cells
  • Detection
  • Diseases And Disorders
  • Epithelial Cells
  • Genetic Phenomena
  • Genetic Variation
  • Genetics
  • Genomic Instability
  • Identification
  • Mammary Glands
  • Medical Personnel
  • Mutations
  • Neoplasms

Fields of Study

  • Medicine

Readers

  • Molecular and genetic basis of cancer.
  • Oncology and Biomarker-Based Cancer Detection.

Technology Areas

  • Biotechnology