title: Spatio-temporal genetic heterogeneity of CTNNB1 mutations in sporadic desmoid type fibromatosis lesions.
abstract: Desmoid type fibromatosis (DT) is a rare lesion of unclear pathogenesis that most often presents a mutation of the (β-catenin) gene. The natural history and clinical evolution are highly variable between patients and to date there is no consensus on optimal therapy. We report two cases of a patient with multiple DT lesions. Molecular investigations performed in both patients on multiple tumors at different anatomical sites revealed non-identical CTNNB1 mutations. The first patient was a 39-year-old man with a history of recurrent DT. In two of the DT lesions, three different mutations were found in codons 41 and 45, respectively. The lesions showed marked inflammatory features, characterized by IgG4 positive lymphoplasmacytic infiltrates and a foreign body reaction, which increased in intensity over time. The patient was eventually treated with a COX-2 inhibitor and the remaining mass was stabilized. In the two DT lesions of the second patient, CTNNB1 mutations S45P and T41A were found. The presence of different mutations in multiple focally recurrent sporadic DT lesions indicates that they do not have a clonal relationship. Our data suggest that a CTNNB1 mutation is a necessary event probably by providing a selective growth advantage. An IgG4 host antigen response is discussed as a potential predisposing factor for one of the patients.
authors.affiliation: Laboratory of Solid Tumours Genetics, Nice University Hospital, 28 Avenue de Valombrose, 06107, Nice, France. jerome.doyen@nice.unicancer.fr.|Institute for Research on Cancer and Aging of Nice (IRCAN), Nice, France. jerome.doyen@nice.unicancer.fr.|Department of Radiation Oncology, Antoine-Lacassagne Center, Nice, France. jerome.doyen@nice.unicancer.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Doyen
authors.affiliation: Laboratory of Solid Tumours Genetics, Nice University Hospital, 28 Avenue de Valombrose, 06107, Nice, France.|Institute for Research on Cancer and Aging of Nice (IRCAN), Nice, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Duranton-Tanneur
authors.affiliation: Department of Biopathology, Institut Bergonié, Bordeaux, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hostein
authors.affiliation: Department of Biopathology, Institut Bergonié, Bordeaux, France.|INSERM U916, Bordeaux, France.|University of Bordeaux, Bordeaux, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Karanian-Philippe
authors.affiliation: Department of Medical Oncology, Institut Universitaire du Cancer Toulouse-Oncopôle, Toulouse, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Chevreau
authors.affiliation: Department of Pathology, Institut Universitaire du Cancer Toulouse-Oncopôle, Toulouse, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Breibach
authors.affiliation: Central Laboratory of Pathology, Nice University Hospital, Nice, France.|Wells NHS Trust Maidstone Hospital Hermitage Lane, Maidstone, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Coutts
authors.affiliation: Laboratory of Solid Tumours Genetics, Nice University Hospital, 28 Avenue de Valombrose, 06107, Nice, France.|Institute for Research on Cancer and Aging of Nice (IRCAN), Nice, France.|Central Laboratory of Pathology, Nice University Hospital, Nice, France.
authors.forename: Bérengère
authors.initials: B
authors.lastname: Dadone
authors.affiliation: Central Laboratory of Pathology, Nice University Hospital, Nice, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Saint-Paul
authors.affiliation: Department of Digestive Surgery and Center for Hepatic Transplantation, Nice University Hospital, Nice, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Gugenheim
authors.affiliation: Medical Oncology Unit, CHU La Timone, Aix-Marseille University, Marseille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Duffaud
authors.affiliation: Laboratory of Solid Tumours Genetics, Nice University Hospital, 28 Avenue de Valombrose, 06107, Nice, France.|Institute for Research on Cancer and Aging of Nice (IRCAN), Nice, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Pedeutour
mesh_terms: D000328:Adult; D000368:Aged; D002467:Cell Nucleus / Q000473:pathology; D003062:Codon / Q000378:metabolism; D005260:Female; D018222:Desmoid Tumors / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D009154:Mutation / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D003062:Codon; D007074:Immunoglobulin G; D051176:beta Catenin
keywords: Desmoid tumor; IgG4; Mesenteric tumor; Sporadic mutation; β-Catenin