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Activating somatic FGFR2 mutations in breast cancer
Nadine Reintjes1, Yun Li, Alexandra Becker
1Institute of Human Genetics, University of Cologne, Cologne, Germany.
Plos One
|March 26, 2013
Summary
Fibroblast growth factor receptor 2 (FGFR2) gene mutations can increase breast cancer risk. This study found a specific FGFR2 mutation (p.K660N) in a breast tumor, showing increased activity that promotes cancer growth.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Fibroblast growth factor receptor 2 (FGFR2) gene variations are known risk factors for breast cancer.
- FGFR2 and its ligand FGF10 are overexpressed in a subset of breast tumors, suggesting their role in tumorigenesis.
Purpose of the Study:
- To investigate somatic mutations and copy number variations in FGFR2 and FGF10 in sporadic breast cancer.
- To functionally characterize a novel somatic FGFR2 mutation (p.K660N) in breast cancer.
Main Methods:
- Sequencing of key FGFR2 coding regions in 140 sporadic breast cancer tumor samples.
- Multiplex Ligation-dependent Probe Amplification (MLPA) for FGFR2 and FGF10 copy number analysis.
- In vitro kinase assays to assess the activity of mutated FGFR2 proteins.
Main Results:
- One somatic heterozygous missense mutation, p.K660N, was identified in the FGFR2 tyrosine kinase domain.
- The p.K660N mutation, along with another known mutation (p.R203C), showed significantly increased intrinsic tyrosine kinase activity.
- Mutant FGFR2 proteins led to elevated phosphorylation and activity of downstream signaling pathways.
Conclusions:
- This study provides the first functional evidence for activating somatic mutations in FGFR2 in breast cancer pathogenesis.
- The findings highlight the role of aberrant FGFR2 signaling in driving tumor development and suggest FGFR2 as a potential therapeutic target.
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