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Recurrent read-through fusion transcripts in breast cancer.

Katherine E Varley1, Jason Gertz, Brian S Roberts

  • 1HudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL, 35806, USA.

Breast Cancer Research and Treatment
|June 16, 2014
PubMed
Summary

Two novel read-through fusion transcripts, SCNN1A-TNFRSF1A and CTSD-IFITM10, were discovered in breast cancer. Targeting the CTSD-IFITM10 fusion reduced cancer cell proliferation, suggesting potential therapeutic targets.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Oncology

Background:

  • Read-through fusion transcripts are a recently identified class of chimeric RNAs formed by splicing adjacent genes in the same orientation.
  • The presence and significance of these fusion transcripts in breast cancer remain largely unexplored.

Purpose of the Study:

  • To investigate the existence and prevalence of read-through fusion transcripts in breast cancer.
  • To identify specific fusion transcripts associated with breast cancer and evaluate their functional impact.

Main Methods:

  • Paired-end RNA sequencing was performed on 168 breast samples, including cell lines, primary tumors (triple-negative and ER-positive), and non-malignant tissues.
  • Bioinformatic analysis was used to identify recurrent read-through fusion transcripts.
  • Western blotting confirmed protein expression, and small interfering RNA (siRNA) experiments assessed functional effects on cell proliferation.

Main Results:

  • Two recurrent read-through fusion transcripts, SCNN1A-TNFRSF1A and CTSD-IFITM10, were identified in breast cancer cell lines and confirmed in primary tumors.
  • These fusion transcripts were not detected in normal breast tissues.
  • The fusion transcripts were translated into proteins, and targeting CTSD-IFITM10 with siRNA reduced breast cancer cell proliferation.

Conclusions:

  • Read-through fusion transcripts represent a novel class of recurrent molecular defects in breast cancer.
  • SCNN1A-TNFRSF1A and CTSD-IFITM10 are potential biomarkers and therapeutic targets for breast cancer.
  • The involvement of membrane proteins suggests these fusions could serve as breast cancer-specific cell surface markers.