Milea Timbergen

60 mutation exhibit a higher recurrence rate after primary resection than wild-type (WT) and T41A mutant tumours 9, 20, 30, 31 and were shown to be more resistant for the NSAID meloxicam 32 . However, others report conflicting results and could not reveal an impact of CTNNB1 mutations on outcome 18, 22 . The molecular mechanisms, underlying a CTNNB1 genotype-phenotype relationship, are not known, although Hamada et al. reported that S45F desmoid cells have a stronger nuclear β-catenin staining in a preclinical model and observed an upregulation of Wnt target genes AXIN2 and CCND1 compared to WT and T41A cells 33 . Here we examined whether the CTNNB1 mutants, encountered in DTF, differentially affect Wnt signalling activity in human desmoids and whether this may explain the variable clinical behaviour between the different CTNNB1 mutants. Materials and methods Dutch and French dataset A Dutch, formalin fixed paraffin embedded (FFPE) DTF cohort (n=64), with CTNNB1 mutation status determined with Sanger sequencing, previously described by van Broekhoven et al. was available for this study 20 . Samples were derived from patients with sporadic, aggressive fibromatosis who underwent surgical excision of their tumour. Clinical characteristics included: sex, tumour localization (extra-abdominal, abdominal wall or intra-abdominal), age at diagnosis and tumour size in millimetres. Additionally, the clinical and molecular data from a French, fresh frozen DTF sample set (n = 128), containing a total of 54613 probe sets, previously described by Salas et al. were accessed through the Gene Expression Omnibus (series matrix file, accession number GSE58697) 34 . This file contains data normalized using the GCRMA algorithm. The data on the CTNNB1 mutations status of these tumours were kindly provided by dr. Frederic Chibon, Cancer Research Center of Toulouse, France. Clinical data included: sex, age at the time of diagnosis, tumour size in millimetres, tumour localization, and tumour status (primary or recurrent). The patient and tumour characteristics of both sample sets are listed in Table 1. 3