Desmoid-type fibromatosis (DTF) has a propensity for locally aggressive behavior. However, a subset of these tumors does not necessarily follow an aggressive clinical course, as rare cases of spontaneous regression and many more examples of tumor quiescence have been reported. Clinical, histopathologic and molecular predictors of DTF outcome remain elusive. Recently, specific mutations of the CTNNB1 gene have been shown to have prognostic significance. This raises the possibility that there are other driver mutations which, in addition to CTNNB1, determine the biological potential of these tumors. Therefore, we propose to use whole exome sequencing of primary, non-syndromic desmoid tumors and adjacent normal tissues to identify other possible driving mutations in DTF.
This project also includes an internal case-control study design, in which primary DTF cases that subsequently recurred locally will be matched and compared to cases unassociated with local recurrence. Identification of additional driver mutations associated with an increased likelihood of local recurrence might assist clinicians and patients faced with difficult management decisions. These altered proteins or their functional pathways might also represent potential pharmacotherapeutic targets.