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Updated: Jan 13, 2026

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Exploring Shootin1's oncogenic role within FGFR2 gene fusions

Volkan Ergin1, Mutlu Erdoğan2, Ekrem Yaşar3

  • 1Division of Biomedical Sciences, University of California, Riverside, USA.

Turkish Journal of Biology = Turk Biyoloji Dergisi
|January 7, 2026
PubMed
Abstract

Insights

A novel Fibroblast Growth Factor Receptor 2 (FGFR2)::Shootin1 (SHTN1) fusion protein drives cancer by constitutively activating FGFR2. This discovery offers new therapeutic targets for challenging malignancies like cholangiocarcinoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Fibroblast Growth Factor Receptor (FGFR) gene fusions are key drivers of cancer initiation and progression.
  • FGFR fusions are significant therapeutic targets, especially in difficult-to-treat cancers such as cholangiocarcinoma.

Purpose of the Study:

  • To characterize the novel FGFR2::SHTN1 fusion.
  • To identify it as a de novo chimeric protein.
  • To elucidate its oncogenic mechanism.

Main Methods:

  • Identification of FGFR2::SHTN1 fusions using cancer genomics databases.
  • Structural modeling with AlphaFold and HADDOCK, including membrane embedding.
  • Assessment of SHTN1 oligomerization and fusion protein activity via coimmunoprecipitation and gel electrophoresis.

Main Results:

  • The FGFR2::SHTN1 fusion is an in-frame joining of FGFR2 exons 1-17 and SHTN1 exons 7-17.
  • The chimeric protein retains the intact FGFR2 tyrosine kinase domain.
  • Shootin1's coiled-coil domains mediate ligand-independent dimerization and constitutive FGFR2 activation.

Conclusions:

  • FGFR2::SHTN1 is a potent oncogenic driver, particularly in cholangiocarcinoma, via constitutive FGFR2 activation.
  • This study provides the first molecular characterization of the FGFR2::SHTN1 fusion.
  • The findings advance understanding of FGFR2 fusion biology and identify a target for future diagnostics and therapies.
Keywords:
FGFR2FGFR2-SHTN1KIAA1598SHTN1cancergene fusion

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