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Updated: Apr 3, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
The FGFR Landscape in Cancer: Analysis of 4,853 Tumors by Next-Generation Sequencing
Teresa Helsten1, Sheryl Elkin2, Elisa Arthur3
1Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center, La Jolla, California. thelsten@ucsd.edu.
Purpose:
Molecular profiling may have prognostic and predictive value, and is increasingly used in the clinical setting. There are more than a dozen fibroblast growth factor receptor (FGFR) inhibitors in development. Optimal therapeutic application of FGFR inhibitors requires knowledge of the rates and types of FGFR aberrations in a variety of cancer types.
Experimental Design:
We analyzed frequencies of FGFR aberrations in 4,853 solid tumors that were, on physician request, tested in a Clinical Laboratory Improvement Amendments (CLIA) laboratory (Foundation Medicine) using next-generation sequencing (182 or 236 genes), and analyzed by N-of-One.
Results:
FGFR aberrations were found in 7.1% of cancers, with the majority being gene amplification (66% of the aberrations), followed by mutations (26%) and rearrangements (8%). FGFR1 (mostly amplification) was affected in 3.5% of 4,853 patients; FGFR2 in 1.5%; FGFR3 in 2.0%; and FGFR4 in 0.5%. Almost every type of malignancy examined showed some patients with FGFR aberrations, but the cancers most commonly affected were urothelial (32% FGFR-aberrant); breast (18%); endometrial (∼13%), squamous lung cancers (∼13%), and ovarian cancer (∼9%). Among 35 unique FGFR mutations seen in this dataset, all but two are found in COSMIC. Seventeen of the 35 are known to be activating, and 11 are transforming.
Conclusions:
FGFR aberrations are common in a wide variety of cancers, with the majority being gene amplifications or activating mutations. These data suggest that FGFR inhibition could be an important therapeutic option across multiple tumor types.
Insights
Fibroblast growth factor receptor (FGFR) aberrations are common in many cancer types, primarily gene amplifications or activating mutations. This suggests FGFR inhibitors may be effective treatments for various solid tumors.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Molecular profiling is crucial for cancer treatment, with numerous fibroblast growth factor receptor (FGFR) inhibitors in development.
- Understanding the prevalence and types of FGFR aberrations is essential for optimizing FGFR inhibitor therapy.
Purpose of the Study:
- To determine the frequencies and types of FGFR aberrations across a broad spectrum of solid tumors.
- To identify specific cancer types with high rates of FGFR aberrations.
Main Methods:
- Next-generation sequencing (182 or 236 genes) was used to analyze FGFR aberrations in 4,853 solid tumors.
- Data from a CLIA-certified laboratory (Foundation Medicine) were analyzed using N-of-One methodology.
Main Results:
- FGFR aberrations were detected in 7.1% of analyzed solid tumors.
- Gene amplification constituted the majority (66%) of aberrations, followed by mutations (26%) and rearrangements (8%).
- Urothelial, breast, endometrial, squamous lung, and ovarian cancers showed the highest prevalence of FGFR aberrations.
Conclusions:
- FGFR aberrations, predominantly gene amplifications and activating mutations, are prevalent across diverse cancer types.
- These findings support the potential of FGFR inhibition as a therapeutic strategy for multiple malignancies.
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