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).

CONCLUSION:

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: J Dômont, S Salas, L Lacroix, V Brouste, P Saulnier, P Terrier, D Ranchère, A Neuville, A Leroux, L Guillou, R Sciot, F Collin, A Dufresne, J-Y Blay, A Le Cesne, J-M Coindre, S Bonvalot, J Bénard
• Journal: British journal of cancer (Br J Cancer) Vol. 102 Issue 6 Pg. 1032-6 (Mar 16 2010) ISSN: 1532-1827 [Electronic] England
• PMID: 20197769 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• beta Catenin

Topics

• Base Sequence
• Biomarkers, Tumor (analysis, genetics)
• DNA Mutational Analysis
• Female
• Fibroma (diagnosis, genetics, therapy)
• Gene Frequency
• Heterozygote
• Humans
• Male
• Molecular Diagnostic Techniques
• Mutation, Missense (physiology)
• Outcome Assessment, Health Care
• Prognosis
• Retrospective Studies
• beta Catenin (genetics, physiology)