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Characterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrier

Johannsson, Oskar T LU ; Staff, Synnöve; Vallon-Christersson, Johan LU ; Kytöla, Soili; Gudjonsson, Thorarinn; Rennstam, Karin LU ; Hedenfalk, Ingrid A LU ; Adeyinka, Adewale LU ; Kjellén, Elisabeth LU and Wennerberg, Johan LU , et al. (2003) In Laboratory Investigation 83(3). p.96-387
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... (More)

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.

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Aneuploidy, Biomarkers, Tumor, Breast Neoplasms, Carcinoma, Ductal, Breast, Codon, Nonsense, DNA, Neoplasm, Female, Flow Cytometry, Genes, BRCA1, Germ-Line Mutation, Heterozygote, Humans, Lymph Nodes, Lymphatic Metastasis, Middle Aged, Nucleic Acid Hybridization, Spectral Karyotyping, Translocation, Genetic, Transplantation, Heterologous, Tumor Cells, Cultured
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Laboratory Investigation
volume
83
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3
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10 pages
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Nature Publishing Group
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  • wos:000181849400010
  • pmid:12649339
  • scopus:0037344346
ISSN
1530-0307
DOI
10.1097/01.LAB.0000060030.10652.8C
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English
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yes
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89600b93-9c6a-4b2e-8450-95b17fa4e699 (old id 112618)
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http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=12649339&dopt=Abstract
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2007-07-09 12:15:48
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2018-05-29 11:52:09
@article{89600b93-9c6a-4b2e-8450-95b17fa4e699,
  abstract     = {<p>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&gt;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.</p>},
  author       = {Johannsson, Oskar T and Staff, Synnöve and Vallon-Christersson, Johan and Kytöla, Soili and Gudjonsson, Thorarinn and Rennstam, Karin and Hedenfalk, Ingrid A and Adeyinka, Adewale and Kjellén, Elisabeth and Wennerberg, Johan and Baldetorp, Bo and Petersen, Ole W and Olsson, Håkan and Oredsson, Stina and Isola, Jorma and Borg, Ake},
  issn         = {1530-0307},
  keyword      = {Aneuploidy,Biomarkers, Tumor,Breast Neoplasms,Carcinoma, Ductal, Breast,Codon, Nonsense,DNA, Neoplasm,Female,Flow Cytometry,Genes, BRCA1,Germ-Line Mutation,Heterozygote,Humans,Lymph Nodes,Lymphatic Metastasis,Middle Aged,Nucleic Acid Hybridization,Spectral Karyotyping,Translocation, Genetic,Transplantation, Heterologous,Tumor Cells, Cultured},
  language     = {eng},
  number       = {3},
  pages        = {96--387},
  publisher    = {Nature Publishing Group},
  series       = {Laboratory Investigation},
  title        = {Characterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrier},
  url          = {http://dx.doi.org/10.1097/01.LAB.0000060030.10652.8C},
  volume       = {83},
  year         = {2003},
}