Genetic and functional diversity of propagating cells in glioblastoma.
Loading...
Embargo End Date
ICR Authors
Authors
Piccirillo, SGM
Colman, S
Potter, NE
van Delft, FW
Lillis, S
Carnicer, M-J
Kearney, L
Watts, C
Greaves, M
Colman, S
Potter, NE
van Delft, FW
Lillis, S
Carnicer, M-J
Kearney, L
Watts, C
Greaves, M
Document Type
Journal Article
Date
2015-01-13
Date Accepted
2014-11-18
Abstract
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.
Citation
Stem cell reports, 2015, 4 (1), pp. 7 - 15
Source Title
Publisher
CELL PRESS
ISSN
2213-6711
eISSN
2213-6711
Collections
Research Team
Biology of Childhood Leukaemia