High frequency of β-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management

• Published in: British journal of cancer 2010-03, Vol.102 (6), p.1032-1036
• Main Authors: Dômont, J, Salas, S, Lacroix, L, Brouste, V, Saulnier, P, Terrier, P, Ranchère, D, Neuville, A, Leroux, A, Guillou, L, Sciot, R, Collin, F, Dufresne, A, Blay, J-Y, Le Cesne, A, Coindre, J-M, Bonvalot, S, Bénard, J
• Format: Article
• Language: English
• Subjects: 631/208/68; 631/67/1857; 692/699/67; Base Sequence; beta Catenin - genetics; beta Catenin - physiology; Biological and medical sciences; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedicine; Cancer Research; DNA Mutational Analysis; Drug Resistance; Epidemiology; Female; Fibroma - diagnosis; Fibroma - genetics; Fibroma - therapy; Gene Frequency; Heterozygote; Humans; Male; Medical sciences; Molecular Diagnostic Techniques; Molecular Diagnostics; Molecular Medicine; Mutation, Missense - physiology; Oncology; Outcome Assessment (Health Care); Prognosis; Retrospective Studies; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605557

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 β -catenin mutations in a European multicentre series of fibromatosis tumours to relate β -catenin mutational status to disease outcome. Methods: Direct sequencing of exon 3 β -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 β -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 β -catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in β -catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P =0.02). Conclusion: A high frequency (87%) of β -catenin mutation hallmarks extra-abdominal fibromatosis from a large multicentric retrospective study. Moreover, wild-type β -catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal fibromatosis.