title: Familial solitary chondrosarcoma resulting from germline EXT2 mutation.
abstract: Germline mutations of EXT2, encoding Exostosin Glycosyltransferase 2, are associated with multiple osteochondromas (MO), an autosomal dominant disease characterized by the development of multiple peripheral cartilaginous benign tumors with a weak risk of malignant transformation. We report here a family with a remarkable clinical presentation characterized by the development of isolated chondrosarcomas, mostly located in ribs. Comparative analysis of exomes from two third-degree affected relatives led us to identify a single common disruptive variation, corresponding to a stop mutation (c.237G > A, p.Trp79*; (NM_000401.3); c.138G > A, p.Trp46*; (NM_207122.1)) within exon 2 of the EXT2 gene. Interestingly, no obvious sign of MO was detected in affected members by radiological examination. This report shows that germline mutations of EXT2 can result, not only in the development of multiple benign osteochondromas, but also in the development of isolated malignant cartilaginous tumors including central tumors, and that the presence of germline EXT2 mutation should be considered in patients suspected to have an inherited predisposition to chondrosarcoma, even in the absence of MO. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Inserm U1079, Faculty of Medicine, UNIROUEN, Normandie Univ and Department of Genetics, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France.
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Heddar
authors.affiliation: Inserm U1079, Faculty of Medicine, UNIROUEN, Normandie Univ and Department of Genetics, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fermey
authors.affiliation: Inserm U1079, Faculty of Medicine, UNIROUEN, Normandie Univ and Department of Genetics, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Coutant
authors.affiliation: Department of Pathology, Rouen University Hospital, Rouen, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Angot
authors.affiliation: Department of Pathology, Rouen University Hospital, Rouen, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Sabourin
authors.affiliation: Department of Radiology, Rouen University Hospital, Rouen, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Michelin
authors.affiliation: Inserm U1079, Faculty of Medicine, UNIROUEN, Normandie Univ and Department of Genetics, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Parodi
authors.affiliation: Inserm U1079, Faculty of Medicine, UNIROUEN, Normandie Univ and Department of Genetics, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Charbonnier
authors.affiliation: Inserm U1079, Faculty of Medicine, UNIROUEN, Normandie Univ and Department of Genetics, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Vezain
authors.affiliation: Inserm U1079, Faculty of Medicine, UNIROUEN, Normandie Univ and Department of Genetics, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Bougeard
authors.affiliation: Inserm U1079, Faculty of Medicine, UNIROUEN, Normandie Univ and Department of Genetics, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Baert-Desurmont
authors.affiliation: Inserm U1079, Faculty of Medicine, UNIROUEN, Normandie Univ and Department of Genetics, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Frébourg
authors.affiliation: Inserm U1079, Faculty of Medicine, UNIROUEN, Normandie Univ and Department of Genetics, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France.
authors.forename: Isabelle
authors.identifier: 0000-0002-5544-048X
authors.initials: I
authors.lastname: Tournier
mesh_terms: D000328:Adult; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology*; D002813:Chondrosarcoma / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D010375:Pedigree; D011379:Prognosis; D000099065:Exostosin 2
chemical_list: D014408:Biomarkers, Tumor; D017351:N-Acetylglucosaminyltransferases; D000099065:Exostosin 2