title: Fibroblast growth factor receptor 2, gain-of-function mutations, and tumourigenesis: investigating a potential link.
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.
authors: Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford OX3 9DS, UK.
authors: Ruth M S
authors: RM
authors: Hansen
authors: Anne
authors: A
authors: Goriely
authors: Steven A
authors: SA
authors: Wall
authors: Ian S D
authors: IS
authors: Roberts
authors: Andrew O M
authors: AO
authors: Wilkie
mesh_terms: D000168:Acrocephalosyndactylia / Q000235:genetics; D000328:Adult; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D013736:Testicular Neoplasms / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D017468:Receptors, Fibroblast Growth Factor; C496353:FGFR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2