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.

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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