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         headline:Genetic variability in MCF-7 sublines: evidence of rapid genomic and RNA expression profile modifications
         description:Both phenotypic and cytogenetic variability have been reported for clones of breast carcinoma cell lines but have not been comprehensively studied. Despite this, cell lines such as MCF-7 cells are extensively used as model systems. In this work we documented, using CGH and RNA expression profiles, the genetic variability at the genomic and RNA expression levels of MCF-7 cells of different origins. Eight MCF-7 sublines collected from different sources were studied as well as 3 subclones isolated from one of the sublines by limit dilution. MCF-7 sublines showed important differences in copy number alteration (CNA) profiles. Overall numbers of events ranged from 28 to 41. Involved chromosomal regions varied greatly from a subline to another. A total of 62 chromosomal regions were affected by either gains or losses in the 11 sublines studied. We performed a phylogenetic analysis of CGH profiles using maximum parsimony in order to reconstruct the putative filiation of the 11 MCF-7 sublines. The phylogenetic tree obtained showed that the MCF-7 clade was characterized by a restricted set of 8 CNAs and that the most divergent subline occupied the position closest to the common ancestor. Expression profiles of 8 MCF-7 sublines were analyzed along with those of 19 unrelated breast cancer cell lines using home made cDNA arrays comprising 720 genes. Hierarchical clustering analysis of the expression data showed that 7/8 MCF-7 sublines were grouped forming a cluster while the remaining subline clustered with unrelated breast cancer cell lines. These data thus showed that MCF-7 sublines differed at both the genomic and phenotypic levels. The analysis of CGH profiles of the parent subline and its three subclones supported the heteroclonal nature of MCF-7 cells. This strongly suggested that the genetic plasticity of MCF-7 cells was related to their intrinsic capacity to generate clonal heterogeneity. We propose that MCF-7, and possibly the breast tumor it was derived from, evolved in a node like pattern, rather than according to a linear progression model. Due to their capacity to undergo rapid genetic changes MCF-7 cells could represent an interesting model for genetic evolution of breast tumors.
         datePublished:2003-04-24T00:00:00Z
         dateModified:2003-04-24T00:00:00Z
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            Comparative Genomic Hybridization
            Comparative Genomic Hybridization Data
            Clonal Heterogeneity
            Comparative Genomic Hybridization Profile
            Cancer Research
            Oncology
            Surgical Oncology
            Health Promotion and Disease Prevention
            Biomedicine
            general
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      headline:Genetic variability in MCF-7 sublines: evidence of rapid genomic and RNA expression profile modifications
      description:Both phenotypic and cytogenetic variability have been reported for clones of breast carcinoma cell lines but have not been comprehensively studied. Despite this, cell lines such as MCF-7 cells are extensively used as model systems. In this work we documented, using CGH and RNA expression profiles, the genetic variability at the genomic and RNA expression levels of MCF-7 cells of different origins. Eight MCF-7 sublines collected from different sources were studied as well as 3 subclones isolated from one of the sublines by limit dilution. MCF-7 sublines showed important differences in copy number alteration (CNA) profiles. Overall numbers of events ranged from 28 to 41. Involved chromosomal regions varied greatly from a subline to another. A total of 62 chromosomal regions were affected by either gains or losses in the 11 sublines studied. We performed a phylogenetic analysis of CGH profiles using maximum parsimony in order to reconstruct the putative filiation of the 11 MCF-7 sublines. The phylogenetic tree obtained showed that the MCF-7 clade was characterized by a restricted set of 8 CNAs and that the most divergent subline occupied the position closest to the common ancestor. Expression profiles of 8 MCF-7 sublines were analyzed along with those of 19 unrelated breast cancer cell lines using home made cDNA arrays comprising 720 genes. Hierarchical clustering analysis of the expression data showed that 7/8 MCF-7 sublines were grouped forming a cluster while the remaining subline clustered with unrelated breast cancer cell lines. These data thus showed that MCF-7 sublines differed at both the genomic and phenotypic levels. The analysis of CGH profiles of the parent subline and its three subclones supported the heteroclonal nature of MCF-7 cells. This strongly suggested that the genetic plasticity of MCF-7 cells was related to their intrinsic capacity to generate clonal heterogeneity. We propose that MCF-7, and possibly the breast tumor it was derived from, evolved in a node like pattern, rather than according to a linear progression model. Due to their capacity to undergo rapid genetic changes MCF-7 cells could represent an interesting model for genetic evolution of breast tumors.
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      dateModified:2003-04-24T00:00:00Z
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         Comparative Genomic Hybridization
         Comparative Genomic Hybridization Data
         Clonal Heterogeneity
         Comparative Genomic Hybridization Profile
         Cancer Research
         Oncology
         Surgical Oncology
         Health Promotion and Disease Prevention
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      name:Equipe Génome et Cancer, UMR 5535 CNRS and EMI 0229 INSERM Centre de Recherche CRLC Val d'Aurelle, Montpellier, France
      name:Equipe Génome et Cancer, UMR 5535 CNRS and EMI 0229 INSERM Centre de Recherche CRLC Val d'Aurelle, Montpellier, France
      name:Equipe Génome et Cancer, UMR 5535 CNRS and EMI 0229 INSERM Centre de Recherche CRLC Val d'Aurelle, Montpellier, France
      name:Equipe Génome et Cancer, UMR 5535 CNRS and EMI 0229 INSERM Centre de Recherche CRLC Val d'Aurelle, Montpellier, France
      name:Equipe Génome et Cancer, UMR 5535 CNRS and EMI 0229 INSERM Centre de Recherche CRLC Val d'Aurelle, Montpellier, France
      name:Laboratoire TAGC, CIML, Université d'Aix-Marseille II, Marseille, France
      name:INSERM U119 and LBT, Institut Paoli Calmette, Marseille, France
      name:Institut des Sciences de l'Evolution de Montpellier CNRS UMR 5554, Université des Sciences et Techniques du Languedoc Montpellier II, Montpellier, France
      name:Equipe Génome et Cancer, UMR 5535 CNRS and EMI 0229 INSERM Centre de Recherche CRLC Val d'Aurelle, Montpellier, France
      name:Institut de Biotechnologies et Pharmacologie CNRS UMR 5094, Faculté de Pharmacie Université Montpellier I, Montpellier, France
      name:Equipe Génome et Cancer, UMR 5535 CNRS and EMI 0229 INSERM Centre de Recherche CRLC Val d'Aurelle, Montpellier, France

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