Loss of heterozygosity and uniparental disomy of chromosome region 10q23.3–26.3 in glioblastoma |
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| Authors: | Ekaterina A. Alekseeva Ekaterina B Kuznetsova Alexander S. Tanas Evgeny V. Prozorenko Anton M. Zaytsev Mikhail I Kurzhupov Olga N. Kirsanova Viktoria V. Rudenko Vladimir V. Strelnikov Dmitry V. Zaletaev |
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| Affiliation: | 1. Laboratory of Epigenetics, Research Centre for Medical Genetics, Moscow, Russia;2. Medical Genetics Laboratory, Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia;3. Human Molecular Genetics Laboratory, Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia;4. Molecular and Cell Genetics Chair, Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, Moscow, Russia;5. Oncology Chair, Faculty of Therapy, Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russia;6. Department of Neurosurgery, Herzen Moscow Oncology Research Institute, Ministry of Health of the Russian Federation, Moscow, Russia |
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| Abstract: | Glioblastoma is the most frequent and aggressive brain tumor in the adult population. Loss of heterozygosity (LOH) at markers of the long arm of chromosome 10 is the most common genetic alteration in glioblastoma, being detectable in up to 80% of cases. We have tested 124 glioblastoma samples for LOH by microsatellite analysis of the 10q23.3–26.3 region which contains the cancer related genes PTEN, FGFR2, MKI67, and MGMT. Then, a real‐time quantitative microsatellite analysis (QuMA) was used to qualitatively estimate the change in copy number of this region in the samples with LOH. LOH was detected in 62.1% of the glioblastoma samples. A total of 64 samples with LOH in this region were examined by QuMA. LOH was attributed to a deletion in 37.5% of cases, and uniparental disomy (UPD) in 25% of cases. In 37.5% of cases, deletion and UPD segments alternated within the region: deletions being more frequent than UPD in its proximal part (encompassing PTEN and FGFR2) and both deletions and UPD occurring at the same frequency in its distal part (MGMT). Thus, we have investigated mechanisms of structural alterations of the chromosome region 10q23.3–26.3 in glioblastoma. In addition to a structural deletion of this region, UPD was identified as a frequent cause of LOH. We resume that more detailed studies of glioblastoma at the molecular genetic level are essential in search for potential markers suitable for predicting the disease outcome and the response to treatment. |
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