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Dynamics of chemosensitivity and chromosomal instability in recurrent glioblastoma
- Source :
- British Journal of Cancer
- Publication Year :
- 2007
- Publisher :
- Springer Science and Business Media LLC, 2007.
-
Abstract
- Glioblastoma multiforme is characterised by invasive growth and frequent recurrence. Here, we have analysed chromosomal changes in comparison to tumour cell aggressiveness and chemosensitivity of three cell lines established from a primary tumour and consecutive recurrences (BTL1 to BTL3) of a long-term surviving glioblastoma patient together with paraffin-embedded materials of five further cases with recurrent disease. Following surgery, the BTL patient progressed under irradiation/ lomustine but responded to temozolomide after re-operation to temozolomide. The primary tumour -derived BTL1 cells showed chromosomal imbalances typical of highly aggressive glioblastomas. Interestingly, BTL2 cells established from the first recurrence developed under therapy showed signs of enhanced chromosomal instability. In contrast, BTL3 cells from the second recurrence resembled a less aggressive subclone of the primary tumour. Although BTL2 cells exhibited a highly aggressive phenotype, BTL3 cells were characterised by reduced proliferative and migratory potential. Despite persistent methylation of the O6-methylguanine-DNA methyltransferase promoter, BTL3 cells exhibited the highest temozolomide sensitivity. A comparable situation was found in two out of five glioblastoma patients, both characterised by enhanced survival time, who also relapsed after surgery/chemotherapy with less aggressive recurrences. Taken together, our data suggest that pretreated glioblastoma patients may relapse with highly chemosensitive tumours confirming the feasibility of temozolomide treatment even in case of repeated recurrence.
- Subjects :
- Cancer Research
Pathology
medicine.medical_specialty
Methyltransferase
chromosomal instability
Dacarbazine
medicine.medical_treatment
Cell
temozolomide
Biology
Cell Line, Tumor
Chromosome instability
Recurrent glioblastoma
medicine
Humans
Molecular Diagnostics
Antineoplastic Agents, Alkylating
Chemotherapy
Temozolomide
Brain Neoplasms
Nucleic Acid Hybridization
Lomustine
Middle Aged
chemosensitivity
medicine.anatomical_structure
Oncology
Drug Resistance, Neoplasm
Cell culture
Cancer research
Female
Neoplasm Recurrence, Local
MGMT
Glioblastoma
medicine.drug
Subjects
Details
- ISSN :
- 15321827 and 00070920
- Volume :
- 96
- Database :
- OpenAIRE
- Journal :
- British Journal of Cancer
- Accession number :
- edsair.doi.dedup.....c50e7ed25b5a92f8439b20fa28bf6bde