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Genetic and Functional Diversity of Propagating Cells in Glioblastoma
Glioblastoma (GBM) is a lethal malignancy whose clinical intransigence has been linked to extensive intraclonal genetic and phenotypic diversity and the common emergence of therapeutic resistance. This interpretation embodies the implicit assumption that cancer stem cells or tumor-propagating cells...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297869/ https://www.ncbi.nlm.nih.gov/pubmed/25533637 http://dx.doi.org/10.1016/j.stemcr.2014.11.003 |
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author | Piccirillo, Sara G.M. Colman, Sue Potter, Nicola E. van Delft, Frederik W. Lillis, Suzanne Carnicer, Maria-Jose Kearney, Lyndal Watts, Colin Greaves, Mel |
author_facet | Piccirillo, Sara G.M. Colman, Sue Potter, Nicola E. van Delft, Frederik W. Lillis, Suzanne Carnicer, Maria-Jose Kearney, Lyndal Watts, Colin Greaves, Mel |
author_sort | Piccirillo, Sara G.M. |
collection | PubMed |
description | Glioblastoma (GBM) is a lethal malignancy whose clinical intransigence has been linked to extensive intraclonal genetic and phenotypic diversity and the common emergence of therapeutic resistance. This interpretation embodies the implicit assumption that cancer stem cells or tumor-propagating cells are themselves genetically and functionally diverse. To test this, we screened primary GBM tumors by SNP array to identify copy number alterations (a minimum of three) that could be visualized in single cells by multicolor fluorescence in situ hybridization. Interrogation of neurosphere-derived cells (from four patients) and cells derived from secondary transplants of these same cells in NOD-SCID mice allowed us to infer the clonal and phylogenetic architectures. Whole-exome sequencing and single-cell genetic analysis in one case revealed a more complex clonal structure. This proof-of-principle experiment revealed that subclones in each GBM had variable regenerative or stem cell activity, and highlighted genetic alterations associated with more competitive propagating activity in vivo. |
format | Online Article Text |
id | pubmed-4297869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-42978692015-01-21 Genetic and Functional Diversity of Propagating Cells in Glioblastoma Piccirillo, Sara G.M. Colman, Sue Potter, Nicola E. van Delft, Frederik W. Lillis, Suzanne Carnicer, Maria-Jose Kearney, Lyndal Watts, Colin Greaves, Mel Stem Cell Reports Report Glioblastoma (GBM) is a lethal malignancy whose clinical intransigence has been linked to extensive intraclonal genetic and phenotypic diversity and the common emergence of therapeutic resistance. This interpretation embodies the implicit assumption that cancer stem cells or tumor-propagating cells are themselves genetically and functionally diverse. To test this, we screened primary GBM tumors by SNP array to identify copy number alterations (a minimum of three) that could be visualized in single cells by multicolor fluorescence in situ hybridization. Interrogation of neurosphere-derived cells (from four patients) and cells derived from secondary transplants of these same cells in NOD-SCID mice allowed us to infer the clonal and phylogenetic architectures. Whole-exome sequencing and single-cell genetic analysis in one case revealed a more complex clonal structure. This proof-of-principle experiment revealed that subclones in each GBM had variable regenerative or stem cell activity, and highlighted genetic alterations associated with more competitive propagating activity in vivo. Elsevier 2014-12-18 /pmc/articles/PMC4297869/ /pubmed/25533637 http://dx.doi.org/10.1016/j.stemcr.2014.11.003 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
spellingShingle | Report Piccirillo, Sara G.M. Colman, Sue Potter, Nicola E. van Delft, Frederik W. Lillis, Suzanne Carnicer, Maria-Jose Kearney, Lyndal Watts, Colin Greaves, Mel Genetic and Functional Diversity of Propagating Cells in Glioblastoma |
title | Genetic and Functional Diversity of Propagating Cells in Glioblastoma |
title_full | Genetic and Functional Diversity of Propagating Cells in Glioblastoma |
title_fullStr | Genetic and Functional Diversity of Propagating Cells in Glioblastoma |
title_full_unstemmed | Genetic and Functional Diversity of Propagating Cells in Glioblastoma |
title_short | Genetic and Functional Diversity of Propagating Cells in Glioblastoma |
title_sort | genetic and functional diversity of propagating cells in glioblastoma |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297869/ https://www.ncbi.nlm.nih.gov/pubmed/25533637 http://dx.doi.org/10.1016/j.stemcr.2014.11.003 |
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