title: Truncation at conserved terminal regions of BRCA1 protein is associated with highly proliferating hereditary breast cancers.
abstract: The existence of two subgroups of BRCA1-associated breast cancer (BC) families has been recently posited: the first with highly proliferating tumors, and the second composed of cases with a low proliferation rate. Our aim was to test whether the proliferation rate of BRCA1-associated breast cancers was affected by the site of the germ line mutation in the BRCA1 gene. We analyzed the distribution of the mitotic index, a histoprognostic grade component shown to segregate in families, matching for germ line mutation location in a series of 28 breast cancers from 20 kindreds. We observed a prevalence of highly proliferating tumors when the mutation occurs in the two terminal conserved domains of the BRCA1 protein, ie., in the amino and carboxyl termini (P = 0.0024). Our data provide evidence for a genotype-phenotype correlation and along with their strong conservation during evolution argue for the importance of these two regions in the control of mammary cell growth.
authors.affiliation: Department of Genetic Oncology and Laboratory of Tumor Biology, Paoli-Calmettes Institute, INSERM U 119, France.
authors.forename: H
authors.initials: H
authors.lastname: Sobol
authors.forename: D
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.forename: B
authors.initials: B
authors.lastname: Bressac-de-Paillerets
authors.forename: J P
authors.initials: JP
authors.lastname: Peyrat
authors.forename: F
authors.initials: F
authors.lastname: Kerangueven
authors.forename: N
authors.initials: N
authors.lastname: Janin
authors.forename: T
authors.initials: T
authors.lastname: Noguchi
authors.forename: F
authors.initials: F
authors.lastname: Eisinger
authors.forename: J M
authors.initials: JM
authors.lastname: Guinebretiere
authors.forename: J
authors.initials: J
authors.lastname: Jacquemier
authors.forename: D
authors.initials: D
authors.lastname: Birnbaum
mesh_terms: D000483:Alleles; D019313:BRCA1 Protein; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000235:genetics; D017384:Sequence Deletion; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D019313:BRCA1 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors