Accession Number:

ADA592383

Title:

Structural Rearrangements in DNA Repair Genes in Breast Cancer

Descriptive Note:

Final rept. 20 Sep 2012-19 Sep 2013

Corporate Author:

PITTSBURGH UNIV PA

Personal Author(s):

Report Date:

2013-10-01

Pagination or Media Count:

9.0

Abstract:

The genetic basis of cancer has been firmly established in the last few decades. Genomic instability is a hallmark feature of virtually all breast cancer cells, and is caused either by inherited mutations in genes that control genomic fidelity and stability particularly in DNA repair pathways, or somatic mutations that are acquired during breast cancer progression. We originally identified translocations in 3 DNA repair genes RAD51C, EYA2, BRIP1 in MCF7 breast cancer cells, and hypothesized that structural genomic alterations in genes that are themselves actually involved in DNA repair enhance the level of genomic instability and ultimately affect breast cancer progression and prognosis. However, we found that these translocations are specific to MCF7 cells private mutations and not present in any other cell lines. Interestingly, we found that BRIP1, a known familial tumor suppressor is amplified in a large portion of sporadic breast cancers. In cells with amplification of BRIP1, knockdown of BRIP1 inhibited cell growth suggesting that BRIP1 might be a driver of breast cancer growth. Mass-spec analysis identified a novel role for BRIP1 as a transcriptional repressor. This study has thus identified a familial tumor suppressor gene which is amplified in sporadic breast cancer and has a novel transcriptional regulatory role.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE