Gliosarcoma: distinct molecular pathways and genomic alterations identified by DNA copy number/SNP microarray analysis

PurposeGliosarcoma is a histologic variant of glioblastoma (GBM), and like GBM carries a poor prognosis. Median survival is less than one (1) year with less than 5% of patients alive after 5years. Although there is no cure, standard treatment includes surgery, radiation and chemotherapy. While very similar to GBM, gliosarcoma exhibits several distinct differences, morphologically and molecularly. Therefore, we report a comprehensive analysis of DNA copy number changes in gliosarcoma using a cytogenomic DNA copy number (CN) microarray (OncoScan((R))).MethodsCytogenomic DNA copy number microarray (OncoScan((R))) was performed on 18 cases of gliosarcoma. MetaCore enrichment was applied to the array results to detect associated molecular pathways.ResultsThe most frequent alteration was copy number loss, comprising 57% of total copy number changes. The number of losses far exceeded the number of amplifications (***, <0.001) and loss of heterozygosity events (***, <0.001). Amplifications were infrequent (4.6%), particularly for EGFR. Chromosomes 9 and 10 had the highest number of losses; a large portion of which correlated to CDKN2A/B loss. Copy number gains were the second most common alteration (26.2%), with the majority occurring on chromosome 7. MetaCore enrichment detected notable pathways for copy number gains including: HOXA, Rho family of GTPases, and EGFR; copy number loss including: WNT, NF-k ss, and CDKN2A; and copy number loss of heterozygosity including: WNT and p53.ConclusionsThe pathways and copy number alterations detected in this study may represent key drivers in gliosarcoma oncogenesis and may provide a starting point toward targeted oncologic analysis with therapeutic potential.