Detection of genomic instability in malignant brain tumors

Abstract

Introduction: Astrocytoma and glioblastoma are the most agressive type of brain tumor. Glioblastoma IDH wild-type is a primary tumor which develops de novo, while Astrocytoma IDH mutant progresses from lower grade tumors. They are characterized by high heterogeneity and resistance to therapy which develop as a consequence of accumulation of mutations that lead to genomic instability. Methods: We analysed genomic instability in 66 patients with malign brain tumors using arbitrarily primed PCR as DNA profiling method. Comparing DNA profiles of tumor and normal (blood) tissues, we detected quantitative and qualitative differences. Quantitative differences are represented by different band intensities and correspond to chromosomal instability (CIN). Qualitative changes seen as band shifts represent microsatellite instability (MIN). We correlated frequencies of genomic instability with tumor gradus and histophatological data. Results: In patients with Glioblastoma IDH wild-type, percentages of high total genomic instability, MIN and CIN were 65%, 32% and 57%, respectfully. In patients with Astrocytoma IDHmutant, percentages of high total genomic instability, MIN and CIN for gradus 3 were 45%, 36% and 72%, respectfully while they were 40%, 40% and 40%, for gradus 4. In patients with NOS (not otherwise specified glioblastoma) percentages are 50%, 50% and 70%, respectfully. Conclusion: Our results show that Glioblastoma IDH wild-type and Astrocytoma IDH mutant gradus 3 have higher genomic instability, while it is lower in Astrocytoma IDH mutant gradus 4. These results are in line with evolutionary theory of origin of cancer. Genomic instability in NOS tumors could be used as a prognostic marker.