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- Title
Gliosarcoma: distinct molecular pathways and genomic alterations identified by DNA copy number/SNP microarray analysis.
- Authors
Lowder, Lindsey; Hauenstein, Jennifer; Woods, Ashley; Chen, Hsiao-Rong; Rupji, Manali; Kowalski, Jeanne; Olson, Jeffrey J.; Saxe, Debra; Schniederjan, Matthew; Neill, Stewart; Weinberg, Brent; Sengupta, Soma
- 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.
- Subjects
RHO GTPases; DNA; DNA analysis; X chromosome
- Publication
Journal of Neuro-Oncology, 2019, Vol 143, Issue 3, p381
- ISSN
0167-594X
- Publication type
Article
- DOI
10.1007/s11060-019-03184-1