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Systematic Detection of Alternative Open Reading Frames (altORFs) in Cancer Driver Genes.

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Title: Systematic Detection of Alternative Open Reading Frames (altORFs) in Cancer Driver Genes.
Authors: Pavesi, Angelo1 (AUTHOR) angelo.pavesi@unipr.it
Source: Journal of Molecular Evolution. Feb2026, Vol. 94 Issue 1, p62-79. 18p.
Subjects: Open reading frames (Genetics), Cancer genes, p53 protein, Ribosomes, Biological databases, Oncogenes, Mass spectrometry
Abstract: The discovery of translated alternative open reading frames (altORFs) in protein-coding regions has expanded the coding potential of viral, prokaryotic and eukaryotic genes. Experimental and computational approaches indicate that overlapping coding regions occur in mammals. In this study, I used a prediction method based on five criteria to detect novel altORFs in the human genes taken from the COSMIC Cancer Gene Census Database. Apart from the well characterized examples of human cancer-specific antigens expressed from altORF, the vast catalogue of nucleotide substitutions across cancer genes (the COSMIC database) is also likely to harbor previously uncharacterized altORFs. Under the five prediction criteria, I found 251 novel altORFs, 41 of which highly conserved in mammals and 60 uniquely resulting from nucleotide substitutions in the primary ORF of cancer genes. I found experimental evidence for 38% of the 251 novel altORFs from mass spectrometry and ribosome profiling databases. In particular, I found three altORFs in the proto-oncogene RET, three expressed altORfs in the isocitrate dehydrogenase-2 gene, and one expressed large altORF (498 nt) in the mutated TP53 gene. This study may offer clinical perspectives, because a potential source of cancer antigens may include antigens derived from translation of currently unannotated open reading frames. The altORFs detected in this study could be candidates for future experimental validation. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Molecular Evolution is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Systematic Detection of Alternative Open Reading Frames (altORFs) in Cancer Driver Genes.
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  Data: <searchLink fieldCode="AR" term="%22Pavesi%2C+Angelo%22">Pavesi, Angelo</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> angelo.pavesi@unipr.it</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Molecular+Evolution%22">Journal of Molecular Evolution</searchLink>. Feb2026, Vol. 94 Issue 1, p62-79. 18p.
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  Data: <searchLink fieldCode="DE" term="%22Open+reading+frames+%28Genetics%29%22">Open reading frames (Genetics)</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+genes%22">Cancer genes</searchLink><br /><searchLink fieldCode="DE" term="%22p53+protein%22">p53 protein</searchLink><br /><searchLink fieldCode="DE" term="%22Ribosomes%22">Ribosomes</searchLink><br /><searchLink fieldCode="DE" term="%22Biological+databases%22">Biological databases</searchLink><br /><searchLink fieldCode="DE" term="%22Oncogenes%22">Oncogenes</searchLink><br /><searchLink fieldCode="DE" term="%22Mass+spectrometry%22">Mass spectrometry</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: The discovery of translated alternative open reading frames (altORFs) in protein-coding regions has expanded the coding potential of viral, prokaryotic and eukaryotic genes. Experimental and computational approaches indicate that overlapping coding regions occur in mammals. In this study, I used a prediction method based on five criteria to detect novel altORFs in the human genes taken from the COSMIC Cancer Gene Census Database. Apart from the well characterized examples of human cancer-specific antigens expressed from altORF, the vast catalogue of nucleotide substitutions across cancer genes (the COSMIC database) is also likely to harbor previously uncharacterized altORFs. Under the five prediction criteria, I found 251 novel altORFs, 41 of which highly conserved in mammals and 60 uniquely resulting from nucleotide substitutions in the primary ORF of cancer genes. I found experimental evidence for 38% of the 251 novel altORFs from mass spectrometry and ribosome profiling databases. In particular, I found three altORFs in the proto-oncogene RET, three expressed altORfs in the isocitrate dehydrogenase-2 gene, and one expressed large altORF (498 nt) in the mutated TP53 gene. This study may offer clinical perspectives, because a potential source of cancer antigens may include antigens derived from translation of currently unannotated open reading frames. The altORFs detected in this study could be candidates for future experimental validation. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Molecular Evolution is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1007/s00239-025-10284-2
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      – Code: eng
        Text: English
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        PageCount: 18
        StartPage: 62
    Subjects:
      – SubjectFull: Open reading frames (Genetics)
        Type: general
      – SubjectFull: Cancer genes
        Type: general
      – SubjectFull: p53 protein
        Type: general
      – SubjectFull: Ribosomes
        Type: general
      – SubjectFull: Biological databases
        Type: general
      – SubjectFull: Oncogenes
        Type: general
      – SubjectFull: Mass spectrometry
        Type: general
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      – TitleFull: Systematic Detection of Alternative Open Reading Frames (altORFs) in Cancer Driver Genes.
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              Text: Feb2026
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              Y: 2026
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