Triple negative breast cancers have a reduced expression of DNA repair genes

PLoS One. 2013 Jun 25;8(6):e66243. doi: 10.1371/journal.pone.0066243. Print 2013.

Abstract

DNA repair is a key determinant in the cellular response to therapy and tumor repair status could play an important role in tailoring patient therapy. Our goal was to evaluate the mRNA of 13 genes involved in different DNA repair pathways (base excision, nucleotide excision, homologous recombination, and Fanconi anemia) in paraffin embedded samples of triple negative breast cancer (TNBC) compared to luminal A breast cancer (LABC). Most of the genes involved in nucleotide excision repair and Fanconi Anemia pathways, and CHK1 gene were significantly less expressed in TNBC than in LABC. PARP1 levels were higher in TNBC than in LABC. In univariate analysis high level of FANCA correlated with an increased overall survival and event free survival in TNBC; however multivariate analyses using Cox regression did not confirm FANCA as independent prognostic factor. These data support the evidence that TNBCs compared to LABCs harbour DNA repair defects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • DNA Repair / genetics*
  • Down-Regulation*
  • Fanconi Anemia / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Homologous Recombination / genetics
  • Humans
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Estrogen / metabolism
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology

Substances

  • RNA, Messenger
  • Receptors, Estrogen

Grants and funding

The work was supported by the Italian Association for Cancer Research (AIRC), Associazione Ricerca in Campo Oncologico (ARCO) and the Victorian Breast Cancer Research Consortium of Australia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.