Loss of heterozygosity and uniparental disomy of chromosome region 10q23.3–26.3 in glioblastoma

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. | I N TR ODU C TI ONGlioblastoma is the most frequent and aggressive brain tumor in the adult population. Glioblastomas account for 80% of primary neoplasms of the central nervous system and are thereby among the most vital problems of neuro-oncology. At the molecular level, glioblastoma has been studied rather comprehensively and is characterized by many genetic and epigenetic alterations, which affect various cancer related genes.1 In spite of the vast data accumulated in the molecular genetics of glioblastoma, only few markers are known to predict the prognosis and response to therapy, the set including abnormal methylation of the MGMT promoter region and IDH1 mutations, which are used in clinical practice.

2b or Not 2b: How Opposing FGF Receptor Splice Variants Are Blocking Progress in Precision Oncology

“…Relevant to brain tumors, the 10q26.13 FGFR2 chromosomal locus is sited adjacent to the WDR11 tumor suppressor gene [198] near the PTEN deletion site at 10q23.31 and the methylatable (repressible) MGMT suppressor gene promoter at 10q26.3 [199] which predicts chemotherapy response and natural history [200][201][202]. Deletion of PTEN leads to mTORC1-induced upregulation of the FGFR2b ligand FGF10, promoting tumor outgrowth [203].…”