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Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
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Identification of targetable FGFR gene fusions in diverse cancers

Yi-Mi Wu1, Fengyun Su, Shanker Kalyana-Sundaram

  • 1Michigan Center for Translational Pathology, University of Michigan Medical School, 1400 E. Medical Center Drive 5316 CCGC, Ann Arbor, MI 48109-5940, USA.

Cancer Discovery
|April 6, 2013
PubMed

Insights

This study identifies Fibroblast Growth Factor Receptor (FGFR) gene fusions in various advanced cancers. These FGFR fusions can be targeted with specific drugs, offering new treatment possibilities for patients.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Gene rearrangements involving Fibroblast Growth Factor Receptor (FGFR) genes are implicated in cancer development.
  • Identifying novel oncogenic drivers is crucial for targeted cancer therapy.

Purpose of the Study:

  • To identify and characterize FGFR gene fusions across diverse advanced cancer types.
  • To investigate the functional consequences and therapeutic potential of FGFR fusions.

Main Methods:

  • Prospective clinical sequencing of advanced cancer patients.
  • Analysis of multiple tumor cohorts for gene rearrangements.
  • Functional assays to assess kinase activity and cell proliferation.
  • In vitro and in vivo drug sensitivity testing.

Main Results:

  • FGFR2 and FGFR3 gene fusions were identified in cholangiocarcinoma, breast, prostate, lung squamous cell, bladder, thyroid, oral cancers, glioblastoma, and head and neck cancers.
  • FGFR fusion proteins exhibit oligomerization capability and induce cell proliferation.
  • Bladder cancer cell lines with FGFR3 fusions showed enhanced sensitivity to targeted inhibition.

Conclusions:

  • FGFR fusions represent a targetable mechanism across a spectrum of cancers.
  • Transcriptome analysis in clinical sequencing is vital for discovering rare, actionable FGFR fusions.
  • Targeted therapies against FGFR fusions hold promise for improved cancer treatment outcomes.

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