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Oncogenic transcription factors and neogenes: New opportunities for cancer immunotherapy?

Elizabeth W Abrash1, J Mauro Calabrese2

  • 1Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, 120 Mason Farm Road, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, 120 Mason Farm Road, Chapel Hill, NC 27599, USA; RNA Discovery Center, University of North Carolina at Chapel Hill, 120 Mason Farm Road, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 120 Mason Farm Road, Chapel Hill, NC 27599, USA.

Molecular Cell
|July 8, 2022
PubMed

Insights

Oncogenic transcription factor fusion proteins create novel RNAs called "neogenes" from silent DNA. These neogenes are potential targets for cancer immunotherapy and may be common in cancer.

Area of Science:

  • Molecular biology
  • Cancer research
  • Genomics

Background:

  • Oncogenic transcription factor (TF) fusions are hallmarks of many cancers.
  • The genomic consequences of TF fusions are not fully understood.

Purpose of the Study:

  • To investigate the functional consequences of oncogenic TF fusions at the genomic level.
  • To identify novel RNA species produced by TF fusions.

Main Methods:

  • Analysis of genomic binding sites for TF fusions.
  • RNA sequencing and analysis to detect novel transcripts.
  • Assessment of RNA processing (splicing, export, translation).

Main Results:

  • Oncogenic TF fusions bind to previously silent genomic regions.
  • These binding events lead to the production of novel RNA transcripts, termed "neogenes".
  • Neogenes are processed (spliced, exported, translated) similarly to normal genes.

Conclusions:

  • Neogenes represent a novel class of cancer-specific transcripts.
  • Neogenes are potential therapeutic targets for cancer immunotherapy.
  • The production of neogenes may be a universal consequence of altered transcription in cancer.

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