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- Title
Novel p53 mutants selected in BRCA-associated tumours which dissociate transformation suppression from other wild-type p53 functions.
- Authors
Smith, P D; Crossland, S; Parker, G; Osin, P; Brooks, L; Waller, J; Philp, E; Crompton, M R; Gusterson, B A; Allday, M J; Crook, T
- Abstract
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
Oncogene, 1999, Vol 18, Issue 15, p2451
- ISSN
0950-9232
- Publication type
Journal Article
- DOI
10.1038/sj.onc.1202565