Genetic and functional diversity of propagating cells in glioblastoma

Sara G.M. Piccirillo, Sue Colman, Nicola E. Potter, Frederik W. Van Delft, Suzanne Lillis, Maria Jose Carnicer, Lyndal Kearney, Colin Watts, Mel Greaves

Research output: Contribution to journalArticle

44 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7-15
Number of pages9
JournalStem Cell Reports
Volume4
Issue number1
DOIs
StatePublished - Jan 13 2015

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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    Piccirillo, S. G. M., Colman, S., Potter, N. E., Van Delft, F. W., Lillis, S., Carnicer, M. J., Kearney, L., Watts, C., & Greaves, M. (2015). Genetic and functional diversity of propagating cells in glioblastoma. Stem Cell Reports, 4(1), 7-15. https://doi.org/10.1016/j.stemcr.2014.11.003