Desmoid tumor is a rare type of tumor of mesenchymal origin, constituting about 0.03% of all cancers. Desmoid tumor can be categorized into either sporadic desmoid tumor or familiar adenomatosis polyposis (FAP), depending on the mutation status of CTNNB1 and APC respectively. It is characterized by well differentiation and overgrowth of connective tissues. Of note, one of the most interesting feature is that desmoid tumor exhibits no metastasis, but instead, is featured by high local invasiveness and recurrence. Many researchers attempted to predict imatinib response using Whole-Exome Sequencing but no significant association was found. In this research, we performed Whole Genome Sequencing on desmoid tumor patients to profile mutations and discover genes or mutations that are associated with sensitivity to imatinib by investigating non-coding regions.
We identified NOTCH2 regulatory mutations as predictor of response of desmoid tumor to imatinib. Deleteriousness of those NOTCH2 mutations was correlated with NOTCH2 expression in an independent cohort. Previous researches suggest that NOTCH signaling pathway is associated with maintenance of mesenchymal stem cell, which has been suggested as the source of desmoid tumor and target of imatinib. Our result indicates that NOTCH2 regulatory mutations and change in NOTCH2 expression can serve as a predictor of response to imatinib in desmoid tumor.