title: Characterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrier.
abstract: A human tumor xenograft (L56Br-X1) was established from a breast cancer axillary lymph node metastasis of a 53-year-old woman with a BRCA1 germ-line nonsense mutation (1806C>T; Q563X), and a cell line (L56Br-C1) was subsequently derived from the xenograft. The xenograft carries only the mutant BRCA1 allele and expresses mutant BRCA1 mRNA but no BRCA1 protein as determined by immunoprecipitation or Western blotting. The primary tumor, lymph node metastasis, and xenograft were hypodiploid by DNA flow cytometry, whereas the cell line displayed an aneuploidy apparently developed via polyploidization. Cytogenetic analysis, spectral karyotyping, and comparative genomic hybridization of the cell line revealed a highly complex karyotype with numerous unbalanced translocations. The xenograft and cell line had retained a somatic TP53 missense mutation (S215I) originating from the primary tumors, as well as a lack of immunohistochemically detectable expression of steroid hormone receptors, epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER-2), and keratin 8. Global gene expression analysis by cDNA microarrays supported a correlation between the expression profiles of the primary tumor, lymph node metastasis, xenograft, and cell line. We conclude that L56Br-X1 and L56Br-C1 are useful model systems for studies of the pathogenesis and new therapeutic modalities of BRCA1-induced human breast cancer.
authors.affiliation: Departments of Oncology, University Hospital, Lund, Sweden. oskarjoh@landspitali.is
authors.forename: Oskar T
authors.initials: OT
authors.lastname: Johannsson
authors.forename: Synnöve
authors.initials: S
authors.lastname: Staff
authors.forename: Johan
authors.initials: J
authors.lastname: Vallon-Christersson
authors.forename: Soili
authors.initials: S
authors.lastname: Kytöla
authors.forename: Thorarinn
authors.initials: T
authors.lastname: Gudjonsson
authors.forename: Karin
authors.initials: K
authors.lastname: Rennstam
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Hedenfalk
authors.forename: Adewale
authors.initials: A
authors.lastname: Adeyinka
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kjellén
authors.forename: Johan
authors.initials: J
authors.lastname: Wennerberg
authors.forename: Bo
authors.initials: B
authors.lastname: Baldetorp
authors.forename: Ole W
authors.initials: OW
authors.lastname: Petersen
authors.forename: Håkan
authors.initials: H
authors.lastname: Olsson
authors.forename: Stina
authors.initials: S
authors.lastname: Oredsson
authors.forename: Jorma
authors.initials: J
authors.lastname: Isola
authors.forename: Ake
authors.initials: A
authors.lastname: Borg
mesh_terms: D000782:Aneuploidy; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000235:genetics* / Q000556:secondary; D018389:Codon, Nonsense; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D019398:Genes, BRCA1; D018095:Germ-Line Mutation / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D032681:Spectral Karyotyping; D014178:Translocation, Genetic; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D018389:Codon, Nonsense; D004273:DNA, Neoplasm