A Functional Assay for Allele-Specific BRCA 1/2 mRNA Null Phenotypes in Breast/Ovarian Cancer Families

Abstract

Germline mutations in the BRCA1 and BRCA2 tumor suppressor genes are among the strongest predictors of breast cancer known. Yet their true contribution to breast cancer risk has never been characterized at the molecular level. In particular, mutations that lie outside of the exons sequenced during conventional screening have never been sought. Such hypothetical mutations could include those affecting transcription, mRNA splicing/processing, or mRNA processing. We have devised an assay for identifying such potential null mutations based on analysis of retention of heterozygosity of exonic SNPs in the cDNA pool. Thus far, such mutations do not occur at a frequency comparable to conventional mutations. We have further determined that, in roughly one year, we will have recruited enough patient samples with sufficiently high likelihood of carrying mutations (by BRCAPRO scores) to determine whether such mutations occur at a small percent of the frequency of conventional mutations.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2008
Accession Number
ADA514021

Entities

People

  • James Fackenthal

Organizations

  • University of Chicago

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cells
  • Department Of Defense
  • Diseases And Disorders
  • Frequency
  • Genetic Code
  • Genetic Variation
  • Genetics
  • Mutations
  • Neoplasms
  • Ovarian Cancer
  • Proteins
  • Rna Stability
  • Suppressors

Fields of Study

  • Biology

Readers

  • Molecular and genetic basis of cancer.