title: Identification of novel alternatively spliced BRCA1-associated RING domain (BARD1) messenger RNAs in human peripheral blood lymphocytes and in sporadic breast cancer tissues.
abstract: BARD1 (BRCA1-associated RING domain) is the dominant binding partner of BRCA1 in vivo. The BARD1 gene has been reported to be mutated in a subset of breast and ovarian cancer patients and BARD1 germ-line mutations have been identified in breast cancer patients negative for BRCA1 or BRCA2 gene alterations. In the present study, we show by RT-PCR and direct sequencing analysis the occurrence of seven novel and one previously identified BARD1 splicing variants in human lymphocytes and breast cancers. Two of the eight variants (BARD1delta and BARD1 DeltaRIN) preserve a correct open reading frame and could encode BARD1 internally deleted proteins, while the remaining six variants display premature stop codons. Characterization of the relative expression of BARD1 FL, BARD1delta, and BARD1 DeltaRIN using quantitative PCR analysis indicated that the mean expression levels of BARD1 FL, BARD1delta, and BARD1 DeltaRIN were significantly higher in tumors than in morphologically normal tissues and lymphocytes. However, we were unable to identify either qualitatively or quantitatively tumor-specific expression patterns of the identified BARD1 splicing variants.
authors.affiliation: Division of Surgical, Molecular and Ultrastructural Pathology, Department of Oncology, University of Pisa and Pisa University Hospital, Via Roma 57, 56126 Pisa, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Lombardi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Falaschi
authors.forename: Claudio
authors.initials: C
authors.lastname: Di Cristofano
authors.forename: Antonio Giuseppe
authors.initials: AG
authors.lastname: Naccarato
authors.forename: Elisa
authors.initials: E
authors.lastname: Sensi
authors.forename: Paolo
authors.initials: P
authors.lastname: Aretini
authors.forename: Manuela
authors.initials: M
authors.lastname: Roncella
authors.forename: Generoso
authors.initials: G
authors.lastname: Bevilacqua
authors.forename: Maria Adelaide
authors.initials: MA
authors.lastname: Caligo
mesh_terms: D017398:Alternative Splicing; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D018388:Codon, Terminator; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D016366:Open Reading Frames; D012333:RNA, Messenger / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D018388:Codon, Terminator; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases