Co-expression of cancer driver genes: IDH-wildtype glioblastoma-derived tumorspheres

• Published in: Journal of translational medicine Vol. 18; no. 1; p. 482
• Main Authors: Yoon, Seon-Jin, Son, Hye Young, Shim, Jin-Kyoung, Moon, Ju Hyung, Kim, Eui-Hyun, Chang, Jong Hee, Teo, Wan Yee, Kim, Se Hoon, Park, Sahng Wook, Huh, Yong-Min, Kang, Seok-Gu
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.12.2020; BioMed Central; BMC
• Subjects: Brain cancer; Brain Neoplasms - genetics; Cancer; Deoxyribonucleic acid; Development and progression; DNA; DNA methylation; Epidermal growth factor; Epidermal growth factor receptors; Gene expression; Genetic aspects; Genomics; Glioblastoma; Glioblastoma - genetics; Glioblastoma multiforme; Glioma; Health aspects; Humans; Insulin-like growth factor-binding protein 5; Isocitrate dehydrogenase; Isocitrate Dehydrogenase - genetics; Isocitrate dehydrogenase-wildtype glioblastoma; Medical prognosis; Medical research; Medicine, Experimental; Mutation; Mutation - genetics; Neoplasm Recurrence, Local; p53 Protein; Patients; Phosphatase; Physiological aspects; Prognosis; PTEN protein; Receptor-Like Protein Tyrosine Phosphatases, Class 5; Retrospective Studies; Single cell RNAseq; Temozolomide; Transcriptome; Transcriptomics; Tumors; Tumorsphere; South Korea; United States > US; Tumorsphere; Isocitrate dehydrogenase-wildtype glioblastoma; Single cell RNAseq; Transcriptome
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-020-02647-8

Driver genes of GBM may be crucial for the onset of isocitrate dehydrogenase (IDH)-wildtype (WT) glioblastoma (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. 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 (scRNAseq) considering the alteration status of TP53, PTEN, EGFR, and TERT promoter as well as MGMT promoter methylation. Transcriptomic perturbation by temozolomide (TMZ) was examined in the two TSs. 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 < 0.001, R = 0.28) and its association increased in the recurrent tumor (p  < 0.001, R = 0.86). TSs reflected the tissue-level patterns of association between the two genes (p < 0.01, R = 0.59, n = 20). A scRNAseq data of a TS revealed the TERT and TP53 expressing cells are in a same single cell cluster. The driver-enriched cluster dominantly expressed the glioma-associated long noncoding RNAs. Most of the driver-associated genes were downregulated after TMZ except IGFBP5. GBM tissue level expression patterns of EGFR, TERT, PTEN, IDH1, PTPRZ1, and MGMT are observed in the GBM TSs. The driver gene-associated cluster of the GBM single cells were enriched with the glioma-associated long noncoding RNAs.