title: RET gene mutations are not involved in the origin of human testicular seminoma.
abstract: Testicular germ cell cancers are the most common solid malignancies in young men, but their pathogenesis remains undetermined although some epidemiological data have implicated both environmental and genetic factors. Glial cell-derived neurotrophic factor (GDNF) is secreted by Sertoli cells, and promotes germ stem cell proliferation by activating RET, a tyrosine kinase receptor. Over-expression of GDNF in adult transgenic mice induces the development of testicular tumours that mimic human seminoma, the most frequent testicular germ cell tumour. Activating mutations of RET were previously reported in several types of cancer, including thyroid, pituitary, adrenal and melanoma cancer. Both mouse experimental model and clinical studies suggested that mutations or selective polymorphisms of RET might be associated with human seminoma. To verify this hypothesis, we conducted this study in a French University Hospital and carried out an association study using tissue samples from 66 paraffin-embedded seminoma tumours. The most frequently mutated exons of the RET proto-oncogene were sequenced to identify mutations or selective polymorphisms. No somatic mutations were identified. The polymorphic variants frequencies did not differ from those in a control Caucasian population. Human classical seminoma that occurs in young men does not appear to be linked with mutations or relevant polymorphisms of RET.
authors.affiliation: Department of Endocrinology and Reproductive Medicine, Centre Hospitalier Universitaire L'Archet, Nice Cedex, France.
authors.forename: N
authors.initials: N
authors.lastname: Chevalier
authors.forename: A
authors.initials: A
authors.lastname: Barlier
authors.forename: C
authors.initials: C
authors.lastname: Roche
authors.forename: B
authors.initials: B
authors.lastname: Mograbi
authors.forename: P
authors.initials: P
authors.lastname: Camparo
authors.forename: M
authors.initials: M
authors.lastname: Devouassoux-Shisheboran
authors.forename: J-F
authors.initials: JF
authors.lastname: Michiels
authors.forename: M
authors.initials: M
authors.lastname: Nebout
authors.forename: D
authors.initials: D
authors.lastname: Chevallier
authors.forename: M
authors.initials: M
authors.lastname: Benahmed
authors.forename: A
authors.initials: A
authors.lastname: Enjalbert
authors.forename: P
authors.initials: P
authors.lastname: Fénichel
mesh_terms: D000818:Animals; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D018239:Seminoma / Q000235:genetics*; D013736:Testicular Neoplasms / Q000235:genetics
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human