Abstract 2885
Background
Glioblastoma is the most common and aggressive primary brain tumor in adults. The most common genetic alteration in glioblastoma is the loss of heterozygosity (LOH) of the chromosome 10q. However LOH merely reflects allelic imbalance in the area without detailed information on the gene copy number.
Methods
We have been the first to conduct a targeted analysis of LOH at the 10q23.3-26.3 chromosome region which contains candidate genes PTEN, FGFR2, MKI67 and MGMT in glioblastoma. A panel of microsatellite markers to detect LOH in the area under study, which includes 20 microsatellite polymorphisms, has been developed and characterized. In order to assess copy number alterations at the 10q23.3-26.3 region in glioblastoma samples with identified LOH, we have developed a system for quantitative microsatellite analysis (QuMA). QuMA is based on amplification of microsatellite loci that contain (CA)n repeats where the repeat itself is the target for hybridization by the fluorescently labeled probe. The reference pool contains primer pairs for six genomic regions located on different chromosomes in which copy number violations are not typical for glioblastoma.
Results
Frequency of LOH at the 10q23.3-26.3 region evaluated in glioblastoma samples equals 62,1% (77/124). In 37,5% (24/64) of the samples only one copy of 10q23.3-26.3 chromosome region was found (deletion), in 25,0% (16/64) two copies were detected (acquired uniparental disomy, aUPD). In 37,5% (24/64) of the samples areas of alternation of deletion and aUPD throughout the tested region were identified. Higher frequencies of deletions were characteristic for the proximal part of 10q23.3-26.3 region (PTEN and FGFR2 genes), while aUPDs were more frequent in the distal part (MGMT gene). Thus, the transition from a region with deletion to a region with aUDP occurs at 10q26.1 - 10q26.2.
Conclusions
Thus, we have shown that the LOH at the 10q23.3-26.3 region in glioblastoma can reflect either a deletion or an aUPD. Detailed study of copy number changes at the 10q23.3-26.3 chromosome region containing PTEN, FGFR2, MKI67 and MGMT will allow to discover new targets for drugs and molecular markers of disease prognosis and response to therapy.
Clinical trial identification
No the trial protocol number
Legal entity responsible for the study
The research was supported by RFBR grant 14-04-031832 mol_a
Funding
Russian Foundation for Basic Research
Disclosure
All authors have declared no conflicts of interest.