Accession Number:

ADA518123

Title:

A Search for Gene Fusions/Translocations in Breast Cancer

Descriptive Note:

Annual rept. 1 Sep 2008-31 Aug 2009

Corporate Author:

MICHIGAN UNIV REGENTS ANN ARBOR DIV OF RESEARCH DEVELOPMENT AND ADMINISTRATION

Personal Author(s):

Report Date:

2009-10-01

Pagination or Media Count:

71.0

Abstract:

We have undertaken a systematic evaluation of breast cancer to map disease-specific, recurrent chromosomal or transcriptional chimeras in breast cancer towards development of novel biomarkers and therapeutic targets. Analysis of in-house and publicly available gene expression and array comparative genomic hybridization aCGH data lead to the discovery that a subset of estrogen receptor positive breast cancers overexpress angiotensin II receptor, type 1 AGTR1. In experimental model systems- both in vitro as well as in xenografts in mice, AGTR1 overexpressing breast cancers are sensitive to losartan, an AGTR1 antagonist that is used to treat high blood pressure. These studies published recently in PNAS have generated much interest in the community and will be followed up by us and others. Towards systematic gene fusion discovery, we have developed paired end transcriptome sequencing protocols and bioinformatic pipeline to nominate gene fusion candidates, also published recently in PNAS. Promising gene fusion candidates from breast cancer cell lines and tissues will be followed up in recurrence screens and functional characterization. Another major advance this year has been the discovery of the role of micro RNA 101 in regulating the expression of histone methyltransferase EZH2 in aggressive breast and prostate cancer, published in Science.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE