Co-expression of cancer driver genes: IDH-wildtype glioblastoma-derived tumorspheres
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Journal of Translational Medicine Open Access
RESEARCH
Co‑expression of cancer driver genes: IDH‑wildtype glioblastoma‑derived tumorspheres Seon‑Jin Yoon1,2, Hye Young Son3, Jin‑Kyoung Shim4, Ju Hyung Moon4, Eui‑Hyun Kim4, Jong Hee Chang4, Wan Yee Teo5,6,7,8, Se Hoon Kim9, Sahng Wook Park1,2, Yong‑Min Huh1,3,10,11*† and Seok‑Gu Kang4,12*†
Abstract Background: Driver genes of GBM may be crucial for the onset of isocitrate dehydrogenase (IDH)-wildtype (WT) glio‑ blastoma (GBM). However, it is still unknown whether the genes are expressed in the identical cluster of cells. Here, we have examined the gene expression patterns of GBM tissues and patient-derived tumorspheres (TSs) and aimed to find a progression-related gene. Methods: We retrospectively collected primary IDH-WT GBM tissue samples (n = 58) and tumor-free cortical tissue samples (control, n = 20). TSs are isolated from the IDH-WT GBM tissue with B27 neurobasal medium. Associations among the driver genes were explored in the bulk tissue, bulk cell, and a single cell RNAsequencing techniques (scR‑ NAseq) considering the alteration status of TP53, PTEN, EGFR, and TERT promoter as well as MGMT promoter methyla‑ tion. Transcriptomic perturbation by temozolomide (TMZ) was examined in the two TSs. Results: We comprehensively compared the gene expression of the known driver genes as well as MGMT, PTPRZ1, or IDH1. Bulk RNAseq databases of the primary GBM tissue revealed a significant association between TERT and TP53 (p
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