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Published on: July 31, 2017
Non-Association of Driver Alterations in PTEN with Differential Gene Expression and Gene Methylation in IDH1 Wildtype
Mrinmay Kumar Mallik1, Kaushik Majumdar2, Shiraz Mujtaba3
1Department of Laboratory Medicine, Mubarak Al Kabeer Hospital, P.O. Box 43787, Hawally 32052, Kuwait.
Abstract:
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 PTEN 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 PTEN-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 PTEN. 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.
Insights
Driver alterations (DAs) in most genes studied impact gene expression and methylation in glioblastoma. However, PTEN alterations showed a unique lack of association with these changes, offering new insights into gliomagenesis.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Driver alterations (DAs) are key in cancer development, influencing cellular processes.
- Analyzing DAs' effects on transcriptome, methylome, and proteome is crucial for understanding oncogenesis.
- Isocitrate Dehydrogenase 1 wildtype glioblastomas (IDH1-W-GBs) present a distinct subtype for molecular investigation.
Purpose of the Study:
- To investigate the modulatory effects of 12 common driver genes on transcriptome and methylome in IDH1-W-GBs.
- To identify differentially expressed mRNAs (DEMs), differentially methylated genes (DMGs), and differentially expressed proteins (DEPs) associated with DAs.
- To characterize the unique behavior of PTEN alterations in IDH1-W-GBs.
Main Methods:
- Utilized The Cancer Genomics Atlas Firehose Legacy Study Group (TCGA-FL-SG) data for Glioblastomas (GBs).
- Generated sample groups with and without DAs in 12 common driver genes using Cbioportal.
- Compared samples for DEMs, DMGs, and DEPs to analyze molecular modulations.
Main Results:
- DAs in all studied driver genes, except PTEN, were associated with significant DEMs and DMGs.
- PTEN DAs were uniquely unassociated with differential gene expression or methylation in IDH1-W-GBs.
- This PTEN characteristic remained consistent regardless of concurrent DAs or specific PTEN alteration types.
Conclusions:
- PTEN alterations exhibit distinct molecular behavior in IDH1-W-GBs compared to other common drivers.
- Findings provide insights into gliomagenesis mechanisms and potential therapeutic targets.
- Further research can explore the implications of PTEN's unique role in glioblastoma treatment.
