Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Piccirillo, Sara G.M., Colman, Sue, Potter, Nicola E., van Delft, Frederik W., Lillis, Suzanne, Carnicer, Maria-Jose, Kearney, Lyndal, Watts, Colin, Greaves, Mel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2014
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
_version_ 1782353184122994688
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
work_keys_str_mv AT piccirillosaragm geneticandfunctionaldiversityofpropagatingcellsinglioblastoma
AT colmansue geneticandfunctionaldiversityofpropagatingcellsinglioblastoma
AT potternicolae geneticandfunctionaldiversityofpropagatingcellsinglioblastoma
AT vandelftfrederikw geneticandfunctionaldiversityofpropagatingcellsinglioblastoma
AT lillissuzanne geneticandfunctionaldiversityofpropagatingcellsinglioblastoma
AT carnicermariajose geneticandfunctionaldiversityofpropagatingcellsinglioblastoma
AT kearneylyndal geneticandfunctionaldiversityofpropagatingcellsinglioblastoma
AT wattscolin geneticandfunctionaldiversityofpropagatingcellsinglioblastoma
AT greavesmel geneticandfunctionaldiversityofpropagatingcellsinglioblastoma