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- Title
Co-expression of cancer driver genes: IDH-wildtype glioblastoma-derived tumorspheres.
- 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
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
CANCER genes; LINCRNA; ISOCITRATE dehydrogenase; P16 gene; GENE expression; GLIOBLASTOMA multiforme; RESEARCH; GENETIC mutation; RESEARCH methodology; GLIOMAS; CANCER relapse; PHOSPHATASES; PROGNOSIS; RETROSPECTIVE studies; MEDICAL cooperation; EVALUATION research; BRAIN tumors; COMPARATIVE studies; OXIDOREDUCTASES
- Publication
Journal of Translational Medicine, 2020, Vol 18, Issue 1, p1
- ISSN
1479-5876
- Publication type
journal article
- DOI
10.1186/s12967-020-02647-8