title: A new alternative splice variant of BRCA1 containing an additional in-frame exon.
abstract: The breast/ovarian cancer susceptibility gene BRCA1 interact with multiple protein complexes involved in cellular mechanisms, such as DNA repair, transcription, homologous recombination and cell cycle regulation. Extensive analyses over the past decade led to the detection of several BRCA1 alternative splice variants. Here, we identify the first BRCA1 alternative splice variant containing an additional in-frame exon. This previously unknown exon 13A-containing transcript is generated by the insertion of 66 nucleotides between exons 13 and 14, due to alternative splicing in intron 13 (IVS13-2786-2720). Furthermore, exon 13A-containing transcript was detectable in total RNA samples from 12 normal tissues and several breast and other cancer cell lines. As revealed by real-time PCR analysis, this transcript corresponds to 20 to 25% of the total BRCA1 mRNA expression levels in leukocytes, brain and cerebellum tissues, whereas its relative level of expression is less than 5% in other tested tissues and cancer cell lines. This novel alternative transcript adds 22 amino acids after residue 1452, thus modifying the primary structure of the trans-activation domain 1 (AD1) and the protein-protein interacting domain of BRCA1 with BRCA2, AR and MSH2. No sequence variant has been detected by direct genomic sequencing of exon 13A in individuals originating from high-risk breast/ovarian cancer families.
authors.affiliation: Cancer Genomics Laboratory T3-57, Oncology and Molecular Endocrinology Research Center, CHUL Research Center, Centre Hospitalier Universitaire de Québec, 2705 Laurier Boulevard, Québec City, Canada.
authors.forename: Jessyka
authors.initials: J
authors.lastname: Fortin
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Moisan
authors.forename: Martine
authors.initials: M
authors.lastname: Dumont
authors.forename: Gilles
authors.initials: G
authors.lastname: Leblanc
authors.forename: Yvan
authors.initials: Y
authors.lastname: Labrie
authors.forename: Francine
authors.initials: F
authors.lastname: Durocher
authors.forename: Paul
authors.initials: P
authors.lastname: Bessette
authors.forename: Peter
authors.initials: P
authors.lastname: Bridge
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Chiquette
authors.forename: Rachel
authors.initials: R
authors.lastname: Laframboise
authors.forename: Jean
authors.initials: J
authors.lastname: Lépine
authors.forename: Bernard
authors.initials: B
authors.lastname: Lespérance
authors.forename: Roxanne
authors.initials: R
authors.lastname: Pichette
authors.forename: Marie
authors.initials: M
authors.lastname: Plante
authors.forename: Louise
authors.initials: L
authors.lastname: Provencher
authors.forename: Patricia
authors.initials: P
authors.lastname: Voyer
authors.forename: Jacques
authors.initials: J
authors.lastname: Simard
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D019313:BRCA1 Protein / Q000235:genetics*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics; D045744:Cell Line, Tumor; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1 / Q000502:physiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics; D014018:Tissue Distribution
chemical_list: D019313:BRCA1 Protein