Only missense mutations affecting the DNA binding domain of p53 influence outcomes in patients with breast carcinoma

PLoS One. 2013;8(1):e55103. doi: 10.1371/journal.pone.0055103. Epub 2013 Jan 24.

Abstract

The presence of a TP53 gene mutation can influence tumour response to some treatments, especially in breast cancer. In this study, we analysed p53 mRNA expression, LOH at 17p13 and TP53 mutations from exons 2 to 11 in 206 patients with breast carcinoma and correlated the results with disease-free and overall survival. The observed mutations were classified according to their type and location in the three protein domains (transactivation domain, DNA binding domain, oligomerization domain) and correlated with disease-free and overall survival. In our population, neither p53 mRNA expression nor LOH correlated with outcome. Concerning TP53 mutations, 27% of tumours were mutated (53/197) and the presence of a mutation in the TP53 gene was associated with worse overall survival (p = 0.0026) but not with disease-free survival (p = 0.0697), with median survival of 80 months and 78 months, respectively. When alterations were segregated into mutation categories and locations, and related to survival, tumours harbouring mutations other than missense mutations in the DNA binding domain of P53 had the same survival profiles as wild-type tumours. Concerning missense mutations in the DNA binding domain, median disease-free and overall survival was 23 months and 35 months, respectively (p = 0.0021 and p<0.0001, respectively), compared with 78 and 80 months in mutated tumours overall. This work shows that disease-free and overall survival in patients with a frameshift mutation of TP53 or missense mutation in the oligomerization domain are the same as those in wild-type TP53 patients.

MeSH terms

  • Binding Sites
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / therapy
  • Chromosomes, Human, Pair 17
  • DNA-Binding Proteins / metabolism*
  • Female
  • Humans
  • Loss of Heterozygosity
  • Middle Aged
  • Mutation, Missense*
  • Real-Time Polymerase Chain Reaction
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • DNA-Binding Proteins
  • Tumor Suppressor Protein p53

Grant support

FV was financially supported by l’Association pour la Recherche contre le Cancer. RB was financially supported by the Conseil Régional de Bourgogne, and by grants from La Ligue contre le Cancer de Côte d’Or and La Ligue contre le Cancer de l’Yonne. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.