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Updated: Oct 20, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Comprehensive identification of FGFR1-4 alterations in 5 557 Chinese patients with solid tumors by next-generation
Weiquan Gu1, Jie Yang1, Yong Wang2,3
1Department of Thoracic Surgery, The First People's Hospital of Foshan Foshan 528041, Guangdong, China.
Abstract:
Deregulation of fibroblast growth factor receptor (FGFR) network is common in cancer due to activating mutations, gene amplifications and chromosomal translocations. Currently, various FGFR inhibitors are being developed. In order to optimize their clinical applications, understanding the frequencies and types of FGFR alterations in multiple cancer types appears to be extremely important. This study characterized FGFR1-4 alterations in solid tumors by next-generation sequencing (NGS). Between Jun. 2019 and Aug. 2020, the sequencing data of 5 557 solid tumors of diverse types in the database of Simcere Diagnostics, Inc. (Nanjing, China) were retrospectively analyzed. A panel-based NGS assay was used to detect FGFR1-4 alterations in tumor samples. 9.2% of cancer cases had FGFR1-4 alterations, in which gene amplifications (51.5%) and mutations (40.7%) were frequent, whereas gene rearrangements were less common (10.0%). FGFR1 was involved in 4.6% of 5 557 cases, FGFR2 in 2.1%, FGFR3 in 1.6%, and FGFR4 in 1.4%. Of patients with FGFR1-4 alterations, TP53, MUC16, NSD3, MYC and LRP1B genes were the top 5 mutant genes. FGFR1-4 aberrations occurred in almost every type of solid tumors, with the most common tumor being endometrial carcinoma (22.2%), followed by sarcoma (17.3%), breast cancer (13.2%), gastric cancer (12.2%), and more. 0.6% of cancer cases harbored FGFR1-4 fusions, with the most common fusion partner being TACC3. Two cases of GBM harboring FGFR3-TACC3 fusions were responsive to anlotinib treatment. In conclusion, FGFR1-4 alterations are prevalent in solid tumors of diverse types, with the majority being gene amplifications and mutations. FGFR1-4 fusions only occur in a minority of cancer cases, and those with glioblastoma harboring FGFR3-TACC3 fusions may benefit from anlotinib.
Insights
Fibroblast growth factor receptor (FGFR) alterations, mainly gene amplifications and mutations, are prevalent in 9.2% of diverse solid tumors. FGFR fusions, though rare, show potential therapeutic response in glioblastoma.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Fibroblast growth factor receptor (FGFR) network deregulation is a significant driver in various cancers.
- Activating mutations, gene amplifications, and chromosomal translocations commonly affect FGFR signaling pathways.
- Optimizing FGFR inhibitor therapies necessitates a comprehensive understanding of FGFR alteration frequencies and types across different cancer types.
Purpose of the Study:
- To characterize the spectrum of FGFR1-4 alterations in a large cohort of solid tumors.
- To determine the prevalence and types of FGFR alterations (mutations, amplifications, rearrangements, fusions) in diverse solid tumor types.
- To identify common co-occurring mutations and potential therapeutic implications of specific FGFR alterations.
Main Methods:
- Retrospective analysis of next-generation sequencing (NGS) data from 5,557 solid tumors.
- Utilized a panel-based NGS assay to detect FGFR1-4 alterations.
- Analyzed sequencing data from Simcere Diagnostics database between June 2019 and August 2020.
Main Results:
- Overall, 9.2% of analyzed solid tumors exhibited FGFR1-4 alterations.
- Gene amplifications (51.5%) and mutations (40.7%) were the most frequent alteration types, with rearrangements occurring in 10.0%.
- FGFR1 alterations were most common (4.6%), followed by FGFR2 (2.1%), FGFR3 (1.6%), and FGFR4 (1.4%). Endometrial carcinoma (22.2%), sarcoma (17.3%), and breast cancer (13.2%) showed high frequencies. FGFR fusions, including FGFR3-TACC3, were identified in 0.6% of cases, with two glioblastoma patients responding to anlotinib.
Conclusions:
- FGFR1-4 alterations are widespread across diverse solid tumors, primarily as gene amplifications and mutations.
- FGFR fusions represent a smaller subset of alterations but hold therapeutic significance, as exemplified by anlotinib response in FGFR3-TACC3 fusion-positive glioblastoma.
- These findings underscore the importance of comprehensive FGFR profiling for guiding targeted therapy selection in oncology.
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