TP53 mutations in familial breast cancer: Functional aspects

Date
2003
Authors
Gasco, M.
Yulug, I. G.
Crook, T.
Advisor
Instructor
Source Title
Human Mutation
Print ISSN
1059-7794
Electronic ISSN
Publisher
John Wiley & Sons, Inc.
Volume
21
Issue
3
Pages
301 - 306
Language
English
Type
Article
Journal Title
Journal ISSN
Volume Title
Abstract

Mutation in p53 (TP53) remains one of the most commonly described genetic events in human neoplasia. The occurrence of mutations is somewhat less common in sporadic breast carcinomas than in other cancers, with an overall frequency of about 20%. There is, however, evidence that p53 is mutated at a significantly higher frequency in breast carcinomas arising in carriers of germ-line BRCA1 and BRCA2 mutations. Some of the p53 mutants identified in BRCA1 and BRCA2 mutation carriers are either previously undescribed or infrequently reported in sporadic human cancers. Functional characterization of such mutants in various systems has revealed that they frequently possess properties not commonly associated with those occurring in sporadic cases: they retain apoptosis-inducing, transactivating, and growth-inhibitory activities similar to the wild-type protein, yet are compromised for transformation suppression and also possess an independent transforming phenotype. The occurrence of such mutants in familial breast cancer implies the operation of distinct selective pressures during tumorigenesis in BRCA-associated breast cancers.

Course
Other identifiers
Book Title
Keywords
Apoptosis, BRCA1, BRCA2, Breast cancer, Cancer, LFS, Li- Fraumeni syndrome, p53, TP53, Transactivation, Tumor, BRCA1 protein, BRCA2 protein, Protein p53, Breast cancer, Carcinogenesis, Familial disease, Gene function, Gene mutation, Genetic analysis, Heterozygote, Human, Nucleotide sequence, Phenotype, Priority journal, Review, Apoptosis, BRCA1 Protein, BRCA2 Protein, Breast neoplasms, Family health, Female, Humans, Mutation, Tumor suppressor protein p53
Citation
Published Version (Please cite this version)