BACKGROUND: Diffuse astrocytomas are characterized by their highly variable biological behavior. The possibility that tumors develop novel aberrations, with relevant biological properties, is often neglected. In this study, we present two cases of diffuse astrocytoma in which additional cytogenetic and epigenetic markers with potential influence on cell proliferation or differentiation were detected at relapse. FINDINGS: The biopsies taken from the primary and recurrent tumors of two patients were analyzed with molecular methods to detect copy number variations (CNVs), gene mutations and epigenetic changes. Both cases were characterized by the R132H mutation in the isocitrate dehydrogenase 1 (IDH1) gene. Features typical of astrocytomas, such as copy-neutral loss of heterozygosity at 17p and the deletion of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, were also detected in both cases. These markers were present in the primary and recurrent lesions. Other aberrations, predominantly deletions or amplifications of chromosomal segments and the hypermethylation of gene promoters, were detected in the recurrent lesions. CONCLUSIONS: The IDH1 mutation was the primary event, as previously reported. According to our observations, the methylation of promoters constituted later events, which may have further disrupted cell proliferation and/or differentiation, together with additional CNVs.

Center of Oncocytogenetics Institute of Medical Biochemistry and Laboratory Diagnostics General University Hospital and 1st Faculty of Medicine Charles University Prague U Nemocnice 449 2 128 08 Prague 2 Czech Republic

Center of Oncocytogenetics Institute of Medical Biochemistry and Laboratory Diagnostics General University Hospital and 1st Faculty of Medicine Charles University Prague U Nemocnice 449 2 128 08 Prague 2 Czech Republic ; Institute of Hematology and Blood Transfusion Nemocnice 2094 1 128 20 Prague 2 Czech Republic

Department of Neurosurgery Central Military Hospital and 1st Faculty of Medicine Charles University U Vojenske nemocnice 1200 169 02 Prague 6 Czech Republic

Institute of Hematology and Blood Transfusion Nemocnice 2094 1 128 20 Prague 2 Czech Republic

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