Article
Molecular effects of local chemotherapy in recurrent glioblastoma
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Authors
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Barbara Klink
- Institut für Klinische Genetik, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany
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Katja Robel
- Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Germany
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Karl Hackmann
- Institut für Klinische Genetik, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany
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Evelin Schrock
- Institut für Klinische Genetik, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany
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Gabriele Schackert
- Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Germany
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Dietmar Krex
- Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Germany
| Published: | September 16, 2010 |
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Outline
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Objective: Carmustine wafers (Gliadel™) are the only available local therapy for glioma treatment and are frequently used for recurrent glioblastomas. Although the therapeutic effect has been shown for primary and recurrent glioblastomas in phase II and III studies, respectively; there are only few data about the effect on the molecular integrity of those alkylating agents in glioma tissue. Therefore we performed this array-based analysis of glioblastoma patients before and after Gliadel™ treatment.
Methods: Patients with resectable recurrent glioblastoma after primary resection and standard radio-chemotherapy were pre-selected. The tumor was resected and Gliadel™ wafers were implanted. Tumor tissue was snap frozen and stored. Those patients, who had no additional treatment until further recurrence and had a third tumor resection were selected for the study. Array-CGH using the 244k Agilent chip was performed to analyse the pre- and post-wafer implantation tissue as well as the primary tumor.
Results: Pre- and post wafer implantation tumor pairs of 7 patients were analyzed successfully using Array-CGH. In another 4 patients, DNA extraction of tumor tissue after wafer implantation resulted in insufficient DNA quality and therefore those cases had to be excluded. H&E stained sections of frozen tissue revealed significant amounts of tumor necrosis in those probes. The most frequent genetic aberrations found in 7 glioblastomas were gain of chromosome 7 (6/7), loss of chromosome 10 (6/7) and gain of chromosome 19 (4/7). The most frequently identified amplification involved the EGFR gene locus on 7p12 (3/7). Comparison of the genetic changes pre- and post wafer implantation revealed a similar appearance for most aberrations, but with additional changes after local chemotherapy. We could not identify any special chromosomal region typical involved after local chemotherapy. We currently verify the Array-CGH results by FISH analyses and PCR analyses, which will also be presented.
Conclusions: Local chemotherapy with alkylating agents in glioblastomas was not associated with particular genetic changes. The significance of the additional aberrations in tumors after local chemotherapy has to be further evaluated.
