Elimination of BRAF p.V600E under selective pressure of BRAF-targeted therapy and expansion of a PIK3CA p.E542K clone in a patient with recurrent malignant glomus tumor

Abstract Glomus tumors are rare mesenchymal tumors that resemble modified smooth muscle cells of the normal glomus body. BRAF p.V600E has previously been detected in glomus tumors and is associated with more aggressive clinical behavior. Here, we report a case of a patient with a malignant BRAF-mutant glomus tumor that initially responded to BRAF targeted therapy, likely leading to the elimination of the clone harboring the BRAF p.V600E. Notably, upon disease progression, BRAF p.V600E was not detected in multiple regions of the recurrent tumor, whereas another clone harboring PIK3CA p.E542K expanded, highlighting the complex genomic landscape of malignant glomus tumors under the selective pressure of targeted therapy.