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Updated: Jun 16, 2026

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
11:48

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition

Published on: October 9, 2014

Alternative splicing regulates FGGY-derived neoantigen presentation and promotes immune evasion in

Li Na Zhao1, Jesper B Andersen1

  • 1Department of Health and Medical Sciences, Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.

Iscience
|June 15, 2026
PubMed

The elucidation of actionable, tumor-specific neoantigens remains a challenge in cancer immunotherapy. We identify FGGY-204, an alternatively spliced isoform of FGGY, as a source of tumor-specific neoantigen presentation. FGGY-204 expression is elevated in HCC and encodes a cryptic peptide that is derived from the primate-specific exon 12. This neoantigen candidate peptide is repressed in the normal liver parenchyma by a multifaceted regulatory program, where the FGGY exon 12 locus is epigenetically silenced by abrogated active chromatin marks and DNA methylation. Exon 12 inclusion is directly suppressed by HNRNPA1, whose silencing promotes FGGY-204 biogenesis, revealing a repressive mechanism with potential in therapy. Critically, FGGY-204 expression defines immune-cold HCC tumors, inversely correlated with CD8+ T cell tumor infiltration and antigen presentation. Its immune association dynamically shifts in response to immunotherapy. FGGY-204 presents a neopeptide, a potential immunotherapeutic target, revealing its precise molecular mechanism of control as an entry point to modulate tumor immunogenicity.

Keywords:
CancerIn silico biology

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