title: The Brca1 and Brca2 proteins and tumor pathogenesis.
abstract: Germline alterations of the BRCA1 or BRCA2 genes result in susceptibility to breast and ovarian cancer. Protein-protein interaction studies, transcription activity and mouse knockout experiments have suggested that the Brca1 and Brca2 proteins are of importance in DNA repair and maintenance of genome integrity, possibly due to the transactivation function of Brca1 or Brca2. Subsequently, tumors in individuals carrying germline mutation in either BRCA1 or BRCA2 gene show instability at chromosomal and gene level. Chromosomal and gene alterations are more pronounced in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic tumors. Furthermore, BRCA1 and BRCA2 mutated breast tumors differ from sporadic tumors in respect to histological phenotype. Typically, a higher grade of malignancy is observed in familial tumors. This review summarizes the putative functions of the Brca1 and Brca2 proteins and pathogenesis in tumors of BRCA1 and BRCA2 mutation carriers.
authors.affiliation: Department of Pathology, University Hospital of Iceland, Reykjavik, Iceland. siguring@rsp.is
authors.forename: S
authors.initials: S
authors.lastname: Ingvarsson
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors