title: Is TP53 dysfunction required for BRCA1-associated carcinogenesis?
abstract: The identification of the breast/ovarian susceptibility genes, BRCA1 and BRCA2 was an important advancement in the field of breast and ovarian cancer research. About 40-50% of site specific hereditary breast cancers and up to 80% of hereditary breast-ovarian cancers result from mutations in the BRCA1 gene. Although BRCA1 mediates multiple functions in the cell, including a role in DNA damage repair and gene transcription, the role of BRCA1 has not completely been elucidated yet. It has been suggested that mutational inactivation of TP53 may be required for BRCA1-associated tumorigenesis. Several studies have shown that TP53 is more frequently inactivated in BRCA1-associated tumors than in sporadic breast or ovarian cancer. Up to 90% of BRCA1-associated tumors harbor either a TP53 mutation and/or TP53 protein accumulation. The remaining tumors may well have other alterations affecting the cell cycle checkpoint. Loss of this checkpoint may be obligatory for BRCA1-tumorigenesis. In this review, we discuss recent advances in BRCA1-research and stress the pivotal role TP53 may play in BRCA1-associated carcinogenesis.
authors.affiliation: Department of Medical Oncology, University Hospital Rotterdam, Josephine Nefkens Institute, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Schuyer
authors.forename: E M
authors.initials: EM
authors.lastname: Berns
mesh_terms: D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D016158:Genes, p53; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D024682:BRCA2 Protein; D005819:Genetic Markers; D009363:Neoplasm Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53