Artikel
Targeted genetic profiling of recurrent glioblastoma: Stem cell markers & MGMT-Status
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Veröffentlicht: | 4. Juni 2012 |
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Gliederung
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Objective: Glioblastoma, the most common and most malignant primary brain tumor, consists of a large proportion of tumor cells and a small proportion of tumor stem cells. Tumor stem cells can be characterized by stem cell markers. However, their number and meaning is mostly unknown. Systemic examinations on paired specimens from initial and recurrent glioblastoma concerning this issue are rare.
Methods: 10 glioblastoma (WHO grade IV) patients were included who underwent macroscopically total tumor removal at initial craniotomy and at least one re-craniotomy for local tumor recurrence. Fresh frozen samples were analyzed by Real-time RT-PCR array (RT2 Profiler PCR Array “Human Stem cells”, Biomol, Hamburg/Germany, n = 3 patients). Selected markers were also examined using real-time RT-PCR (n = 10 patients).
Results: Array analysis revealed ≥ 2 fold expression in at least 2 glioblastoma recurrences for the following genes: (1) APC (tumor suppressor protein which is involved in cell migration, cell adhesion and apoptosis) and (2) PARD6A (cell membrane protein involved in cell devision and astrocyte migration). 21 additional markers were overexpressed in one of three recurrences each. Real-time RT-PCR of 9 markers in 10 patients revealed ≥ 2 fold expression of the following markers: APC (n = 4/10), CXCR4 (n = 4/10), PARD6A (n = 2), Nestin (n = 1/10), SOX-2 (n = 1/10). The MGMT-status was positive in 3 patients, changed from positive to negative status in 2 patients and was negative in 5 patients.
Conclusions: A distinct subset of glioblastoma patients shows marked elevation of stem cell markers in recurrent lesions. These markers are of potential interest in terms of future treatment. This project is supported by the "Stiftung Neurochirurgische Forschung" of the "DGNC" and the "Familie Mehdorn Stiftung" in Kiel.