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Tumor-associated epilepsy and glioma: are there common genetic pathways?
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. (neurologi)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. (neurologi)
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2009 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 48, no 7, 955-963 p.Article, review/survey (Refereed) Published
Abstract [en]

Background. Patients with glioma exhibit a great variability in clinical symptoms apart from variations in response to therapy and survival. Many patients present with epileptic seizures at disease onset, especially in case of low-grade gliomas, but not all have seizures. A large proportion of patients develop refractory seizures. It is likely that the variability in epileptic symptoms cannot exclusively be explained by tumor-related factors, but rather reflects complex interaction between tumor-related, environmental and hereditary factors. Material and methods. No data exist on susceptibility genes associated with epileptic symptoms in patients with glioma. However, an increasing number of candidate genes have been proposed for other focal epilepsies such as temporal lobe epilepsy. Some of the susceptibility candidate genes associated with focal epilepsy may contribute to epileptic symptoms also in patients with glioma. Results. This review presents an update on studies on genetic polymorphisms and focal epilepsy and brings forward putative candidate genes for tumor-associated epilepsy, based on the assumption that common etiological pathways may exist for glioma development and glioma-associated seizures. Conclusion. Genes involved in the immune response, in synaptic transmission and in cell cycle control are discussed that may play a role in the pathogenesis of tumor growth as well as epileptic symptoms in patients with gliomas.

Place, publisher, year, edition, pages
2009. Vol. 48, no 7, 955-963 p.
National Category
Medical and Health Sciences
Research subject
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-108658DOI: 10.1080/02841860903104145ISI: 000271228400002OAI: oai:DiVA.org:uu-108658DiVA: diva2:236788
Available from: 2009-09-25 Created: 2009-09-25 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Towards Novel Biomarkers for Low-grade Glioma
Open this publication in new window or tab >>Towards Novel Biomarkers for Low-grade Glioma
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Gliomas are common primary brain tumours that occur as low-grade (LGG) and high-grade gliomas (HGG). Typically occurring in younger adults, LGG has an indolent course with a median survival of 5-10 years, but carries an inherent potential for transforming into HGG. The thesis focused on LGG in adults, with the aim of identifying prognostic biomarkers for LGG.

Paper I. Epileptic seizures are common symptoms in LGG. In a retrospective study, the correlation between 11C-methionine (MET) uptake, measured by Positron Emission Tomography (PET), and seizure activity was assessed in 101 patients with LGG. Although there was no correlation between MET uptake and seizure activity, survival was longer in patients who were seizure-free before surgery.

Paper II. This finding prompted the search for common genetic pathways for both tumour and seizure development and a review of genetic polymorphisms in focal epilepsy and glioma risk. Cell cycle and immune response genes affecting both glioma and seizure risk were identified, and genes involved in synaptic transmission presented potential candidates for future studies.

Paper III. The transcription factor PROX1 plays a pivotal role in normal development and carcinogenesis of various organs. The prognostic value of PROX1, together with established clinical and molecular prognostic factors for survival, was retrospectively assessed in 116 patients with LGG. High PROX1 expression in the tumour was associated with shorter survival.

Paper IV. DNA repair enzymes, such as ERCC6, are crucial for maintaining genomic stability in glioma response to radiotherapy. An association between the polymorphism rs4253079, mapped to ERCC6, and longer survival in patients with LGG and HGG was identified.

Paper V. As LGG typically presented as non-contrast enhancing tumours on morphological MRI (magnetic resonance imaging), the value of combined MET PET with physiological MRI for preoperative diagnosis was assessed in a prospective study of 32 patients with suspected LGG. Representative tumour areas were identified through a combination of perfusion-MRI with MET PET, which can be used as a baseline investigation for follow-up over time.

Conclusions: The parameters seizure-freedom before surgery, the polymorphism rs4253079 in ERCC6 and low PROX1 expression in the tumor were identified as favorable prognostic biomarkers.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 70 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 834
Keyword
Low-grade glioma, prognosis, epilepsy, PROX1, DNA repair enzyme, PET, Physiological MRI
National Category
Medical and Health Sciences
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-183363 (URN)978-91-554-8518-4 (ISBN)
Public defence
2012-12-10, Rosénsalen, Akademiska sjukhuset, ing. 95, Uppsala, 13:00 (Swedish)
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Available from: 2012-11-19 Created: 2012-10-24 Last updated: 2013-01-23Bibliographically approved

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Berntsson, ShalaSmits, Anja

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