Novel p53 mutants selected in BRCA-associated tumours which dissociate transformation suppression from other wild-type p53 functions

Oncogene. 1999 Apr 15;18(15):2451-9. doi: 10.1038/sj.onc.1202565.


Inheritance of germ-line mutant alleles of BRCA1 and BRCA2 confers a markedly increased risk of breast cancer and we have previously reported a higher incidence of p53 mutations in these tumours than in grade matched sporadic tumours. We have now characterized these p53 mutants. The results of these studies identify a novel class of p53 mutants previously undescribed in human cancer yet with multiple occurrences in BRCA-associated tumours which retain a profile of p53-dependent activities in terms of transactivation, growth suppression and apoptosis induction which is close or equal to wild-type. However, these mutants fail to suppress transformation and exhibit gain of function transforming activity in rat embryo fibroblasts. These mutants therefore fall into a novel category of p53 mutants which dissociate transformation suppression from other wild-type functions. The rarity of these mutants in human cancer and their multiple occurrence in BRCA-associated breast tumours suggests that these novel p53 mutants are selected during malignant progression in the unique genetic background of BRCA1- and BRCA2-associated tumours.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • BRCA1 Protein / genetics*
  • BRCA2 Protein
  • Breast Neoplasms / genetics*
  • Carcinoma / genetics
  • Cell Transformation, Neoplastic / genetics
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics
  • Embryo, Mammalian / cytology
  • Female
  • Fibroblasts
  • Gene Expression Regulation, Neoplastic
  • Genetic Complementation Test
  • Humans
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Rats
  • Suppression, Genetic
  • Transcription Factors / genetics*
  • Transcriptional Activation
  • Tumor Suppressor Protein p53 / genetics*


  • BRCA1 Protein
  • BRCA2 Protein
  • CDKN1A protein, human
  • Cdkn1a protein, rat
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Neoplasm Proteins
  • Transcription Factors
  • Tumor Suppressor Protein p53