gms | German Medical Science

61st Annual Meeting of the German Society of Neurosurgery (DGNC) as part of the Neurowoche 2010
Joint Meeting with the Brazilian Society of Neurosurgery on the 20 September 2010

German Society of Neurosurgery (DGNC)

21 - 25 September 2010, Mannheim

Stem like cell populations derived from human glioblastomas carry genetic alterations commonly found in malignant gliomas and advanced neuroblastomas

Meeting Abstract

  • Angelika Gutenberg - Abteilung für Neurochirurgie, Georg-August-Universität Göttingen, Germany
  • Ella Kim - Abteilung für Neurochirurgie, Georg-August-Universität Göttingen, Germany
  • Christina Enders - Gastroenteropathologie, Georg-August-Universität Göttingen, Germany
  • Veit Rohde - Abteilung für Neurochirurgie, Georg-August-Universität Göttingen, Germany
  • Laszlo Füzesi - Gastroenteropathologie, Georg-August-Universität Göttingen, Germany
  • Alf Giese - Abteilung für Neurochirurgie, Georg-August-Universität Göttingen, Germany

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocV1624

DOI: 10.3205/10dgnc097, URN: urn:nbn:de:0183-10dgnc0970

Published: September 16, 2010

© 2010 Gutenberg et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

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Objective: Malignant brain tumours contain a distinct sub-population of tumorigenic cells generally termed “brain tumour initiating cells” (BTICs) that possess biological features of adult neural stem cells. The ability to repopulate the entire tumour and confer radio- and chemo-resistance clearly identifies BTICs as the prime cell target for therapy of malignant brain tumours. This study was carried out to show the chromosomal changes that characterize BTICs before and after irradiation.

Methods: TICs were isolated from established GBM primary cultures. Radioresistant cell populations were selected by exposing BTICs cultures to repetitive rounds of clinically relevant doses of ionizing radiation (IR). The tumorigenic potential of the BTICs was confirmed by using an orthotopic glioma mouse model. Six BTIC and their radioresistant cultures were analyzed using comparative genetic hybridization (CGH).

Results: All 12 cell cultures revealed chromosomal changes. Radioresistant BTICs revealed higher mean copy number netto changes than primary BTCIs (17.83 ± 2.89 versus 15.0 ± 2.46). The increase in copy number changes was due to more chromosomal gains (10.83 ± 2.44 versus 7.83 ± 1,64) after irradiation. Chromosomal gains in primary and irradiated BTCIs were seen on whole chromosome 7 (100%) and 1q (83.3%). Gain of 17q was more frequently found in irradiated BTCIs (83.3% vs 50%). Losses in primary and irradiated BTCIs were mainly to 10p (66.7%), 10q (50%) and 9p (50%). Losses on 1p (50% vs 16.7%) were more frequently observed in irradiated BTICs .

Conclusions: BTICs share the common cytogenetic changes observed in high grade gliomas. Higher chromosomal instability mirrors the invasive behaviour and accelerated tumour progression after irradiation. The gain of 17q and loss of 1p might reflect adverse prognostic factors as seen in neuroblastomas of advanced stage.