Activating Somatic FGFR2 Mutations in Breast Cancer
| Autor: | Yun Li, Edyta Rohmann, Rita K. Schmutzler, Nadine Reintjes, Alexandra Becker, Bernd Wollnik |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Somatic cell
Mutant DNA Mutational Analysis Gene Dosage lcsh:Medicine medicine.disease_cause Germany Basic Cancer Research Pathology Missense mutation lcsh:Science Mutation Multidisciplinary integumentary system Cancer Risk Factors Protein-Tyrosine Kinases Oncology Medicine Female Tyrosine kinase Research Article Signal Transduction musculoskeletal diseases congenital hereditary and neonatal diseases and abnormalities Clinical Pathology Genetic Causes of Cancer Immunoblotting Molecular Sequence Data Mutation Missense Breast Neoplasms Biology Molecular Genetics Breast cancer Germline mutation Genetic Mutation Diagnostic Medicine medicine Genetics Cancer Genetics Humans Immunoprecipitation Receptor Fibroblast Growth Factor Type 2 Genetic Association Studies DNA Primers Base Sequence Point mutation lcsh:R Computational Biology Human Genetics medicine.disease Molecular biology stomatognathic diseases HEK293 Cells Genetics of Disease Cancer research Mutagenesis Site-Directed lcsh:Q Fibroblast Growth Factor 10 Multiplex Polymerase Chain Reaction |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 3, p e60264 (2013) |
| ISSN: | 1932-6203 |
| Popis: | It is known that FGFR2 gene variations confer a risk for breast cancer. FGFR2 and FGF10, the main ligand of FGFR2, are both overexpressed in 5-10% of breast tumors. In our study, we sequenced the most important coding regions of FGFR2 in somatic tumor tissue of 140 sporadic breast cancer patients and performed MLPA analysis to detect copy number variations in FGFR2 and FGF10. We identified one somatic heterozygous missense mutation, p.K660N (c.1980G>C), within the tyrosine kinase domain of FGFR2 in tumor tissue of a sporadic breast cancer patient, which is likely mediated by the FGFR2-IIIb isoform. The presence of wild type and mutated alleles in equal quantities suggests that the mutation has driven clonal amplification of mutant cells. We have analyzed the tyrosine kinase activity of p.K660N and another recently described somatic breast cancer mutation in FGFR2, p.R203C, after expression in HEK293 cells and demonstrated that the intrinsic tyrosine kinase activity of both mutant proteins is strongly increased resulting in elevated phosphorylation and activity of downstream effectors. To our knowledge, this is the first report of functional analysis of somatic breast cancer mutations in FGFR2 providing evidence for the activating nature of FGFR2-mediated signalling in the pathogenesis of breast cancer. |
| Databáze: | OpenAIRE |
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