DNMT3A Expression and Hypomethylation as Indicators of Aggressive Genomic Alterations and Poor Outcomes in Lower-Grade Glioma
Document Type
Abstract
Location
Virtual
Start Date
24-4-2026 9:00 AM
End Date
24-4-2026 3:00 PM
Description
Background: Lower-grade gliomas (LGG) exhibit diverse clinical outcomes, with epigenetic alterations increasingly recognized as key drivers of tumor progression. While DNMT3A mediates DNA methylation, its specific role as a transcriptional and epigenetic prognostic marker, and its independent associations with genomic alterations in LGG, remains to be fully elucidated. Methods: We analyzed DNMT3A mRNA expression, DNA methylation, and clinical data from the TCGA LGG (PanCancer Atlas) cohort using cBioPortal. We performed independent comparative analyses based on: (1) DNMT3A mRNA expression levels (High vs. Low) and (2) DNMT3A DNA methylation levels (Low vs. High). Survival outcomes and the frequencies of Copy Number Alterations (CNAs) in CDKN2A/B and EGFR were evaluated for each comparison. Results: High DNMT3A expression was significantly associated with shorter overall survival compared to low expression. Similarly, low DNMT3A methylation (hypomethylation) showed a trend toward poorer outcomes compared to high methylation. Notably, both high expression and low methylation of DNMT3A were consistently associated with a higher prevalence of CDKN2A, CDKN2B, CDKN2A-AS1, and CDKN2B-AS1 depletions, as well as increased amplifications of EGFR and EGFR-AS1. These results indicate that both transcriptional and epigenetic activation of DNMT3A serve as indicators for critical genomic instability in LGG. Conclusions: Our findings suggest that DNMT3A acts as a transcriptionally and epigenetically driven prognostic marker in LGG. The independent associations of high expression and low methylation with CDKN2A/B loss and EGFR amplification highlight DNMT3A as a key molecular axis for risk stratification, reflecting a more aggressive genomic landscape in LGG patients.
Recommended Citation
Ko, Hyunmin, "DNMT3A Expression and Hypomethylation as Indicators of Aggressive Genomic Alterations and Poor Outcomes in Lower-Grade Glioma" (2026). Medicine Research Day. 11.
https://digitalscholar.lsuhsc.edu/mrd/2026/tr/11
DNMT3A Expression and Hypomethylation as Indicators of Aggressive Genomic Alterations and Poor Outcomes in Lower-Grade Glioma
Virtual
Background: Lower-grade gliomas (LGG) exhibit diverse clinical outcomes, with epigenetic alterations increasingly recognized as key drivers of tumor progression. While DNMT3A mediates DNA methylation, its specific role as a transcriptional and epigenetic prognostic marker, and its independent associations with genomic alterations in LGG, remains to be fully elucidated. Methods: We analyzed DNMT3A mRNA expression, DNA methylation, and clinical data from the TCGA LGG (PanCancer Atlas) cohort using cBioPortal. We performed independent comparative analyses based on: (1) DNMT3A mRNA expression levels (High vs. Low) and (2) DNMT3A DNA methylation levels (Low vs. High). Survival outcomes and the frequencies of Copy Number Alterations (CNAs) in CDKN2A/B and EGFR were evaluated for each comparison. Results: High DNMT3A expression was significantly associated with shorter overall survival compared to low expression. Similarly, low DNMT3A methylation (hypomethylation) showed a trend toward poorer outcomes compared to high methylation. Notably, both high expression and low methylation of DNMT3A were consistently associated with a higher prevalence of CDKN2A, CDKN2B, CDKN2A-AS1, and CDKN2B-AS1 depletions, as well as increased amplifications of EGFR and EGFR-AS1. These results indicate that both transcriptional and epigenetic activation of DNMT3A serve as indicators for critical genomic instability in LGG. Conclusions: Our findings suggest that DNMT3A acts as a transcriptionally and epigenetically driven prognostic marker in LGG. The independent associations of high expression and low methylation with CDKN2A/B loss and EGFR amplification highlight DNMT3A as a key molecular axis for risk stratification, reflecting a more aggressive genomic landscape in LGG patients.