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

• Authors: Lindsey Lowder, Emory University; Jennifer Hauenstein, Emory University; Ashley Woods, Emory University; Hsiao-Rong Chen, Emory University; Manali Rupji, Emory University; Jeanne Kowalski, Emory University; Jeffrey Olson, Emory University; Debra Saxe, Emory University; Matthew Schniederjan, Emory University; Stewart Neill, Emory University; Brent Weinberg, Emory University; Soma Sengupta, Emory University
• Journal Title: Journal of Neuro-Oncology
• Volume: Volume 143, Number 3
• Publisher: Springer Verlag (Germany) | 2019-07-01, Pages 381-392
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1007/s11060-019-03184-1
• Subjects: Biology, Neuroscience; Health Sciences, Oncology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Clinical Neurology; Neurosciences & Neurology; Gliosarcoma; Glioblastoma; Glioma; Oncoscan; Microarray; EGFR; HOX GENES; GLIOBLASTOMA; OVEREXPRESSION; EXPRESSION; MUTATIONS; RECEPTOR; CELLS

Abstract

Purpose: Gliosarcoma 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 5 years. 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®). Methods: Cytogenomic DNA copy number microarray (OncoScan®) was performed on 18 cases of gliosarcoma. MetaCore™ enrichment was applied to the array results to detect associated molecular pathways. Results: The 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-kß, and CDKN2A; and copy number loss of heterozygosity including: WNT and p53. Conclusions: The 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.