Furthermore, the combination of hydroxychloroquine and sorafenib enhances the antiproliferative and proapoptotic effects in S45F-mutated DT cells, suggesting that profiling β-catenin status could guide clinical management of desmoid patients who are considering sorafenib treatment.
Primary sporadic DTFs harboring a CTNNB1 S45F mutation have a higher risk of recurrence after surgery compared to T41A, S45P, and WT DTF, but this association seems to be mediated by tumor size.
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.
We demonstrated that mutated DFs (T41A or S45F) and WT are two distinct molecular subgroups with regard to β-catenin stability, α-catenin affinity, and gene expression profiling.
The other 3 patients showed a CTNNB1 mutation in the original desmoid-type fibromatosis (2 with a T41A and 1 with an S45F mutation), which was absent in the sarcoma.