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Updated: Oct 28, 2025

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Exploring the Significance of the Exon 4-Skipping Isoform of the ZNF217 Oncogene in Breast Cancer

Aurélie Bellanger1,2, Diep T Le1,3, Julie Vendrell4

  • 1Université Lyon 1, Lyon, France.

Frontiers in Oncology
|July 19, 2021
PubMed

Insights

This study identifies a new breast cancer biomarker, ZNF217-ΔE4, which, combined with ZNF217-WT, improves prognostic accuracy. This dual signature aids in better breast cancer stratification and clinical decision-making.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Alternative splicing of oncogenes generates functional transcripts, potentially serving as prognostic biomarkers in breast cancer.
  • The ZNF217 oncogene is established, but its exon 4-skipping isoform (ZNF217-ΔE4) lacks clinical and biological investigation.

Purpose of the Study:

  • To investigate the clinical and biological relevance of the ZNF217-ΔE4 splice variant in breast cancer.
  • To explore the potential of ZNF217-ΔE4 and ZNF217-WT as a combined prognostic biomarker.

Main Methods:

  • In silico RNA-seq and RT-qPCR analyses to detect ZNF217-ΔE4 transcripts in primary breast tumors.
  • Retrospective analysis of ZNF217 isoform expression in Luminal breast cancer subtypes.
  • Ectopic expression studies of ZNF217-ΔE4 in breast cancer cell lines.

Main Results:

  • Confirmed the existence of ZNF217-ΔE4 transcripts in breast tumors, correlating positively with ZNF217-WT mRNA levels.
  • A ZNF217-ΔE4-WT gene-expression signature provided enhanced prognostic information in Luminal breast cancer compared to individual isoforms.
  • ZNF217-ΔE4 overexpression promoted an aggressive phenotype and increased ZNF217-WT expression, linked to reduced ZNF217 gene DNA methylation.

Conclusions:

  • The ZNF217-ΔE4 splice variant plays a role in breast cancer, interacting closely with ZNF217-WT.
  • A dual signature combining ZNF217-ΔE4 and ZNF217-WT expression may serve as a novel prognostic biomarker for improved breast cancer stratification and therapeutic decisions.
Keywords:
ZNF217breast cancerisoformprognosissplice variant

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