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Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
High MYC mRNA Expression Is More Clinically Relevant than MYC DNA Amplification in Triple-Negative Breast Cancer
Eriko Katsuta1, Li Yan2, Takashi Takeshita1
1Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Abstract:
DNA abnormalities are used in inclusion criteria of clinical trials for treatments with specific targeted molecules. MYC is one of the most powerful oncogenes and is known to be associated with triple-negative breast cancer (TNBC). Its DNA amplification is often part of the targeted DNA-sequencing panels under the assumption of reflecting upregulated signaling. However, it remains unclear if MYC DNA amplification is a surrogate of its upregulated signaling. Thus, we investigated the difference between MYC DNA amplification and mRNA high expression in TNBCs utilizing publicly available cohorts. MYC DNA amplified tumors were found to have various mRNA expression levels, suggesting that MYC DNA amplification does not always result in elevated MYC mRNA expression. Compared to other subtypes, both MYC DNA amplification and mRNA high expression were more frequent in the TNBCs. MYC mRNA high expression, but not DNA amplification, was significantly associated with worse overall survival in the TNBCs. The TNBCs with MYC mRNA high expression enriched MYC target genes, cell cycle related genes, and WNT/β-catenin gene sets, whereas none of them were enriched in MYC DNA amplified TNBCs. In conclusion, MYC mRNA high expression, but not DNA amplification, reflects not only its upregulated signaling pathway, but also clinical significance in TNBCs.
Insights
High MYC mRNA expression, not DNA amplification, is linked to poorer outcomes in triple-negative breast cancer (TNBC). This finding is crucial for understanding MYC
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- MYC oncogene is implicated in triple-negative breast cancer (TNBC) development.
- MYC DNA amplification is often assumed to correlate with increased MYC signaling.
- The relationship between MYC DNA amplification and actual MYC mRNA expression in TNBC is not well understood.
Purpose of the Study:
- To investigate the correlation between MYC DNA amplification and MYC mRNA high expression in TNBC.
- To determine if MYC DNA amplification serves as a reliable indicator of MYC signaling.
- To assess the clinical significance of MYC DNA amplification versus MYC mRNA high expression in TNBC.
Main Methods:
- Utilized publicly available patient cohorts for TNBC analysis.
- Compared MYC DNA amplification status with MYC mRNA expression levels.
- Analyzed overall survival data in relation to MYC DNA amplification and mRNA expression.
- Performed gene set enrichment analysis for MYC amplified and MYC mRNA high expressing tumors.
Main Results:
- MYC DNA amplification did not consistently correlate with elevated MYC mRNA expression in TNBC.
- Both MYC DNA amplification and high mRNA expression were more prevalent in TNBC compared to other breast cancer subtypes.
- High MYC mRNA expression, but not DNA amplification, was significantly associated with worse overall survival in TNBC patients.
- TNBCs with high MYC mRNA expression showed enrichment of MYC target genes, cell cycle genes, and WNT/β-catenin pathways, unlike those with MYC DNA amplification.
Conclusions:
- MYC mRNA high expression, rather than DNA amplification, accurately reflects upregulated MYC signaling in TNBC.
- High MYC mRNA expression demonstrates significant clinical relevance and prognostic value in TNBC.
- The findings suggest that targeting MYC signaling in TNBC should focus on mRNA expression levels rather than solely on DNA amplification.
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