Contributions to drug resistance in glioblastoma derived from malignant cells in the sub-ependymal zone
Sara Gm Piccirillo, Inmaculada Spiteri, Andrea Sottoriva, Anestis Touloumis, Suzan Ber, Stephen J Price, Richard Heywood, Nicola-Jane Francis, Karen D Howarth, Vincent P Collins, Ashok R Venkitaraman, Christina Curtis, John C Marioni, Simon Tavaré, Colin Watts, Sara Gm Piccirillo, Inmaculada Spiteri, Andrea Sottoriva, Anestis Touloumis, Suzan Ber, Stephen J Price, Richard Heywood, Nicola-Jane Francis, Karen D Howarth, Vincent P Collins, Ashok R Venkitaraman, Christina Curtis, John C Marioni, Simon Tavaré, Colin Watts
Abstract
Glioblastoma, the most common and aggressive adult brain tumor, is characterized by extreme phenotypic diversity and treatment failure. Through fluorescence-guided resection, we identified fluorescent tissue in the sub-ependymal zone (SEZ) of patients with glioblastoma. Histologic analysis and genomic characterization revealed that the SEZ harbors malignant cells with tumor-initiating capacity, analogous to cells isolated from the fluorescent tumor mass (T). We observed resistance to supramaximal chemotherapy doses along with differential patterns of drug response between T and SEZ in the same tumor. Our results reveal novel insights into glioblastoma growth dynamics, with implications for understanding and limiting treatment resistance.
©2014 American Association for Cancer Research.
Figures
![Figure 1. Identification of SEZ in human…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4286248/bin/emss-61174-f0001.jpg)
![Figure 2. The SEZ harbors residual disease](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4286248/bin/emss-61174-f0002.jpg)
![Figure 3. TICs can be isolated from…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4286248/bin/emss-61174-f0003.jpg)
![Figure 4. TICs from SEZ contribute to…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4286248/bin/emss-61174-f0004.jpg)
![Figure 5. Phylogenetic reconstruction reveals different patterns…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4286248/bin/emss-61174-f0005.jpg)
Source: PubMed