B149
Contrasting telomere dynamics between neuronal and glial paediatric brain tumours (on behalf of CCLG Biological Studies Committee)
Ruman Rahman, Lee Ridley, Teresa Osteso-Ibanez, Siobhan Quinn, Beth Coyle, Richard Grundy
University of Nottingham, Nottingham, UK
We and others have previously demonstrated telomerase-mediated telomere maintenance as a key mechanism facilitating tumour progression in childhood Ependymoma. However, telomerase and telomere status of paediatric GBM, sPNET and PNET primary tissue has not been forthcoming, with only limited current data, derived from cell lines.
Here we show that telomerase activity was evident in 7/7 GBM, 8/18 sPNET and 20/20 PNET tumours, consistent with high tumour grade. Telomere length for sPNET DNA (mean 5.2kb) was significantly shorter than those of patient-matched blood (mean 6.3kb). Telomere dynamics was similar for PNET tumour DNA with telomere length significantly shorter (mean 4.4kb) than those of blood (mean 6.9kb). This was in contrast to mean GBM telomere length (mean 8.3kb), comparable to telomere length from blood (mean 8.5kb). Longer telomere length observed for GBM tumours is consistent with our previous findings in ependymoma (mean telomere length 10.9kb). This hints at a fundamental difference in early neurogenesis with respect to cellular replicative history. Our results encourage consideration of varying telomere length dynamics when devising therapeutic strategies for telomerase inhibition. We predict the onset of replicative senescence and apoptosis to occur more rapidly in sPNET and PNET tumours upon telomerase inhibition.
Histone deacteylase (HDAC) inhibitors are a category of telomerase inhibitors being studied as a treatment for cancer and neurodegenerative diseases and proposed to be associated with silencing of gene promoters, including that of hTERT. Our prelimianry evidence shows that TSA inhibits cell proliferation in both sPNET and PNET cell lines and induces apotosis, concomitant with reduction in telomerase activity.
