title: High frequency of beta-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management.
abstract: BACKGROUND
  Fibromatosis comprises distinct clinical entities, including sporadic extra-abdominal fibromatosis, which have a high tendency for recurrence, even after adequate resection. There are no known molecular biomarkers of local recurrence. We searched for beta-catenin mutations in a European multicentre series of fibromatosis tumours to relate beta-catenin mutational status to disease outcome.
  
  
  METHODS
  Direct sequencing of exon 3 beta-catenin gene was performed for 155 frozen fibromatosis tissues from all topographies. Correlation of outcome with mutation rate and type was performed on the extra-abdominal fibromatosis group (101 patients).
  
  
  RESULTS
  Mutations of beta-catenin were detected in 83% of all cases. Among 101 extra-abdominal fibromatosis, similar mutation rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%), and deletion (2%). None of the clinico-pathological parameters were found to be significantly associated with beta-catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in beta-catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P=0.02).
  
  
  CONCLUSIONS
  A high frequency (87%) of beta-catenin mutation hallmarks extra-abdominal fibromatosis from a large multicentric retrospective study. Moreover, wild-type beta-catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal fibromatosis.
authors.affiliation: Sarcoma Committee, Institut Gustave Roussy, Villejuif, France.
authors.forename: J
authors.initials: J
authors.lastname: Dômont
authors.forename: S
authors.initials: S
authors.lastname: Salas
authors.forename: L
authors.initials: L
authors.lastname: Lacroix
authors.forename: V
authors.initials: V
authors.lastname: Brouste
authors.forename: P
authors.initials: P
authors.lastname: Saulnier
authors.forename: P
authors.initials: P
authors.lastname: Terrier
authors.forename: D
authors.initials: D
authors.lastname: Ranchère
authors.forename: A
authors.initials: A
authors.lastname: Neuville
authors.forename: A
authors.initials: A
authors.lastname: Leroux
authors.forename: L
authors.initials: L
authors.lastname: Guillou
authors.forename: R
authors.initials: R
authors.lastname: Sciot
authors.forename: F
authors.initials: F
authors.lastname: Collin
authors.forename: A
authors.initials: A
authors.lastname: Dufresne
authors.forename: J-Y
authors.initials: JY
authors.lastname: Blay
authors.forename: A
authors.initials: A
authors.lastname: Le Cesne
authors.forename: J-M
authors.initials: JM
authors.lastname: Coindre
authors.forename: S
authors.initials: S
authors.lastname: Bonvalot
authors.forename: J
authors.initials: J
authors.lastname: Bénard
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005350:Fibroma / Q000175:diagnosis* / Q000235:genetics* / Q000628:therapy; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D008297:Male; D025202:Molecular Diagnostic Techniques; D020125:Mutation, Missense / Q000502:physiology; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D012189:Retrospective Studies; D051176:beta Catenin / Q000235:genetics* / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; D051176:beta Catenin