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Updated: Aug 17, 2026

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
Published on: December 22, 2020
Fibroblast growth factor receptor 2, gain-of-function mutations, and tumourigenesis: investigating a potential link
Ruth M S Hansen1, Anne Goriely, Steven A Wall
1Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, UK.
Abstract:
Activating germline mutations in the fibroblast growth factor receptor (FGFR) gene family have been identified in several dominantly inherited skeletal disorders; in the case of FGFR3, the same somatically arising mutations have also been isolated from a variety of tumour tissues. Whilst the role of FGFR2 mutations in congenital syndromes has been well documented, their relationship with cancer has not been clearly defined. Based on evidence that gain-of-function mutations in FGFR2 drive positive selection in adult spermatogonia, the present study investigated, by denaturing high-performance liquid chromatography (DHPLC), DNA sequencing, and restriction digestion, the prevalence of FGFR2 mutations in 58 tumour cell lines of various types, and 29 testicular germ cell tumour samples. Although sequence variations and allelic imbalance were identified in FGFR2, none of the previously documented dominant mutations was detected in any of the tumour types examined. This suggests that gain-of-function FGFR2 mutations are not commonly encountered in tumourigenesis and specifically excludes a major contribution in testicular tumours.
Insights
Activating fibroblast growth factor receptor 2 (FGFR2) mutations are not common in tumors. This study found no evidence of dominant FGFR2 mutations in various tumor cell lines or testicular germ cell tumors.
Area of Science:
- Molecular biology
- Genetics
- Oncology
Background:
- Activating germline mutations in fibroblast growth factor receptor (FGFR) genes cause skeletal disorders.
- FGFR3 mutations are found in both inherited disorders and tumors.
- The role of FGFR2 mutations in cancer is not well-defined, despite their known association with congenital syndromes.
Purpose of the Study:
- To investigate the prevalence of fibroblast growth factor receptor 2 (FGFR2) mutations in various tumor types.
- To determine if gain-of-function FGFR2 mutations contribute to tumorigenesis, particularly in testicular germ cell tumors.
Main Methods:
- Analysis of 58 tumor cell lines and 29 testicular germ cell tumor samples.
- Utilized denaturing high-performance liquid chromatography (DHPLC), DNA sequencing, and restriction digestion to detect FGFR2 mutations.
Main Results:
- Sequence variations and allelic imbalance in FGFR2 were identified.
- No previously documented dominant gain-of-function FGFR2 mutations were found in any of the examined tumor types.
- This suggests FGFR2 mutations do not commonly drive tumor formation.
Conclusions:
- Gain-of-function FGFR2 mutations are not frequently observed in tumorigenesis.
- FGFR2 mutations do not appear to play a significant role in the development of testicular germ cell tumors.
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