• Milea J M Timbergen, Matthijs L Janssen, Cornelis Verhoef, Dirk J Grünhagen, Frederic Chibon, Marcel Smid, Stefan Sleijfer, and Wiemer Erik A C EAC Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus Medical Center Rotterdam, the Netherlands. Electronic address: e.wiemer@erasmusmc.
• Department of Surgical Oncology, Erasmus MC Cancer Institute, Erasmus Medical Center Rotterdam, the Netherlands; Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus Medical Center Rotterdam, the Netherlands.
• Eur J Surg Oncol. 2019 Apr 1; 45 (4): 691-698.

IntroductionSporadic desmoid-type fibromatosis (DTF) is a rare soft tissue tumor of mesenchymal origin. It is characterized by local invasive growth and unpredictable growth behavior. Three distinct mutations involving the CTNNB1 (β-catenin) gene have been identified in the vast majority of DTF tumors, which cause activation of the Wnt signaling pathway and impact prognosis. This study examines whether the different CTNNB1 mutants (T41A, S45F) occurring in DTF tumors differentially affect Wnt signaling activity, which might explain the different disease course between DTF patients harboring different CTNNB1 mutations.Materials And MethodsReal-time polymerase chain reaction (RT-PCR) on 61 formalin fixed paraffin embedded DTF samples with known CTNNB1 status was used to measure the relative mRNA expression level of Wnt target genes AXIN2, DKK1 and CCND1. Additionally, publicly available mRNA expression data retrieved from the Gene Expression Omnibus of 128 DTF samples were used for an unsupervised cluster analyses based on the expression of a selection of Wnt targets.ResultsNo statistically significant difference in relative expression levels of Wnt target genes AXIN2, DKK1 and CCND1 was identified between either CTNNB1 wild-type, S45F or T41A mutated DTF samples. Moreover, the hierarchical cluster analyses using selected Wnt targets did not discriminate between different CTNNB1 mutation types.ConclusionsNo differences in the expression levels of Wnt target genes were observed between the different CTNNB1 mutation types in DTF tumors. Further studies are needed to decipher the mechanism accounting for the diverse disease courses between DTF patients with different CTNNB1 variants.Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

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