Non-Association of Driver Alterations in PTEN with Differential Gene Expression and Gene Methylation in IDH1 Wildtype Glioblastomas
During oncogenesis, alterations in driver genes called driver alterations (DAs) modulate the transcriptome, methylome and proteome through oncogenic signaling pathways. These modulatory effects of any DA may be analyzed by examining differentially expressed mRNAs (DEMs), differentially methylated ge...
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MDPI AG
2023-01-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/13/2/186 |
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| author | Mrinmay Kumar Mallik Kaushik Majumdar Shiraz Mujtaba |
| author_facet | Mrinmay Kumar Mallik Kaushik Majumdar Shiraz Mujtaba |
| author_sort | Mrinmay Kumar Mallik |
| collection | DOAJ |
| description | During oncogenesis, alterations in driver genes called driver alterations (DAs) modulate the transcriptome, methylome and proteome through oncogenic signaling pathways. These modulatory effects of any DA may be analyzed by examining differentially expressed mRNAs (DEMs), differentially methylated genes (DMGs) and differentially expressed proteins (DEPs) between tumor samples with and without that DA. We aimed to analyze these modulations with 12 common driver genes in Isocitrate Dehydrogenase 1 wildtype glioblastomas (IDH1-W-GBs). Using Cbioportal, groups of tumor samples with and without DAs in these 12 genes were generated from the IDH1-W-GBs available from “The Cancer Genomics Atlas Firehose Legacy Study Group” (TCGA-FL-SG) on Glioblastomas (GBs). For all 12 genes, samples with and without DAs were compared for DEMs, DMGs and DEPs. We found that DAs in <i>PTEN</i> were unassociated with any DEM or DMG in contrast to DAs in all other drivers, which were associated with several DEMs and DMGs. This contrasting <i>PTEN</i>-related property of being unassociated with differential gene expression or methylation in IDH1-W-GBs was unaffected by concurrent DAs in other common drivers or by the types of DAs affecting <i>PTEN</i>. From the lists of DEMs and DMGs associated with some common drivers other than PTEN, enriched gene ontology terms and insights into the co-regulatory effects of these drivers on the transcriptome were obtained. The findings from this study can improve our understanding of the molecular mechanisms underlying gliomagenesis with potential therapeutic benefits. |
| first_indexed | 2024-03-11T09:05:00Z |
| format | Article |
| id | doaj.art-676a5494644d4e76a955d18a5f2e6a45 |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-11T09:05:00Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
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| series | Brain Sciences |
| spelling | doaj.art-676a5494644d4e76a955d18a5f2e6a452023-11-16T19:27:24ZengMDPI AGBrain Sciences2076-34252023-01-0113218610.3390/brainsci13020186Non-Association of Driver Alterations in PTEN with Differential Gene Expression and Gene Methylation in IDH1 Wildtype GlioblastomasMrinmay Kumar Mallik0Kaushik Majumdar1Shiraz Mujtaba2Department of Laboratory Medicine, Mubarak Al Kabeer Hospital, P.O. Box 43787, Hawally 32052, KuwaitDepartment of Pathology, Al Sabah Hospital, P.O. Box 4078, Shuwaikh Industrial 70051, KuwaitDepartment of Biology, City University of New York, Brooklyn, NY 11225, USADuring oncogenesis, alterations in driver genes called driver alterations (DAs) modulate the transcriptome, methylome and proteome through oncogenic signaling pathways. These modulatory effects of any DA may be analyzed by examining differentially expressed mRNAs (DEMs), differentially methylated genes (DMGs) and differentially expressed proteins (DEPs) between tumor samples with and without that DA. We aimed to analyze these modulations with 12 common driver genes in Isocitrate Dehydrogenase 1 wildtype glioblastomas (IDH1-W-GBs). Using Cbioportal, groups of tumor samples with and without DAs in these 12 genes were generated from the IDH1-W-GBs available from “The Cancer Genomics Atlas Firehose Legacy Study Group” (TCGA-FL-SG) on Glioblastomas (GBs). For all 12 genes, samples with and without DAs were compared for DEMs, DMGs and DEPs. We found that DAs in <i>PTEN</i> were unassociated with any DEM or DMG in contrast to DAs in all other drivers, which were associated with several DEMs and DMGs. This contrasting <i>PTEN</i>-related property of being unassociated with differential gene expression or methylation in IDH1-W-GBs was unaffected by concurrent DAs in other common drivers or by the types of DAs affecting <i>PTEN</i>. From the lists of DEMs and DMGs associated with some common drivers other than PTEN, enriched gene ontology terms and insights into the co-regulatory effects of these drivers on the transcriptome were obtained. The findings from this study can improve our understanding of the molecular mechanisms underlying gliomagenesis with potential therapeutic benefits.https://www.mdpi.com/2076-3425/13/2/186PTENdriver alterationsIDH1 wildtype glioblastomaCbioportaltranscriptomemethylome |
| spellingShingle | Mrinmay Kumar Mallik Kaushik Majumdar Shiraz Mujtaba Non-Association of Driver Alterations in PTEN with Differential Gene Expression and Gene Methylation in IDH1 Wildtype Glioblastomas Brain Sciences PTEN driver alterations IDH1 wildtype glioblastoma Cbioportal transcriptome methylome |
| title | Non-Association of Driver Alterations in PTEN with Differential Gene Expression and Gene Methylation in IDH1 Wildtype Glioblastomas |
| title_full | Non-Association of Driver Alterations in PTEN with Differential Gene Expression and Gene Methylation in IDH1 Wildtype Glioblastomas |
| title_fullStr | Non-Association of Driver Alterations in PTEN with Differential Gene Expression and Gene Methylation in IDH1 Wildtype Glioblastomas |
| title_full_unstemmed | Non-Association of Driver Alterations in PTEN with Differential Gene Expression and Gene Methylation in IDH1 Wildtype Glioblastomas |
| title_short | Non-Association of Driver Alterations in PTEN with Differential Gene Expression and Gene Methylation in IDH1 Wildtype Glioblastomas |
| title_sort | non association of driver alterations in pten with differential gene expression and gene methylation in idh1 wildtype glioblastomas |
| topic | PTEN driver alterations IDH1 wildtype glioblastoma Cbioportal transcriptome methylome |
| url | https://www.mdpi.com/2076-3425/13/2/186 |
| work_keys_str_mv | AT mrinmaykumarmallik nonassociationofdriveralterationsinptenwithdifferentialgeneexpressionandgenemethylationinidh1wildtypeglioblastomas AT kaushikmajumdar nonassociationofdriveralterationsinptenwithdifferentialgeneexpressionandgenemethylationinidh1wildtypeglioblastomas AT shirazmujtaba nonassociationofdriveralterationsinptenwithdifferentialgeneexpressionandgenemethylationinidh1wildtypeglioblastomas |