PDGRFB mutation‐associated myofibromatosis: Response to targeted therapy with imatinib

Abstract

Heterozygous activating mutations in platelet-derived growth factor receptor B (PDGFRB) have been recently identified as a cause of autosomal-dominant infantile myofibromatosis. We describe a 36-year-old man with PDGFRB c.1681C>T (p.R561C) mutation. Upon progressive disease, the patient received treatment with imatinib and showed a remarkable response with remission of multiple lesions after 12 months. This is the first report of an adult patient with PDGFRB c.1681C>T mutation treated with imatinib.imatinib, infantile myofibromatosis, PDGFRB, precision oncology

Odontogenic myxomas lack PDGFRB mutations reported in myofibromas

“…These genetic alterations were detected not only in the soft tissue tumors, but also in the intra-osseous lesions (Table 1). 16,19,[28][29][30] Herein, we did not detect such mutations in any of the 15 odontogenic myxoma samples evaluated, suggesting that these PDGFRB mutations do not play a role in its tumorigenesis.…”

“…Agaimy et al reported PDGFRB somatic mutations as molecular driver events in the majority of sporadic infantile and adult solitary myofibromas (75% and 69%, respectively). These genetic alterations were detected not only in the soft tissue tumors, but also in the intra‐osseous lesions (Table ) . Herein, we did not detect such mutations in any of the 15 odontogenic myxoma samples evaluated, suggesting that these PDGFRB mutations do not play a role in its tumorigenesis.…”

Genetic testing and surveillance in infantile myofibromatosis: a report from the SIOPE Host Genome Working Group

“…At least 20 families have been reported so far, 19 of which carry a heterozygous PDGFRB variant (NM_002609.4): p.Arg561Cys in 15 (79%) of these 19 cases. The same variant was also reported in sporadic cases of IM [5][6][7]. Three families carry unique PDGFRB germline variants that are classified as likely pathogenic: p.Pro560Leu, p.Arg561Ser, and p.Lys567Glu [8][9][10].…”

“…Only one variant, p.Asp850Val, confers full resistance to this compound, suggesting that most patients with PDGFRB-mutant IM may be eligible for imatinib therapy. Two case reports suggest that this drug is effective and well tolerated [5,20]. Side effects include growth retardation, as reported in children with chronic myeloid leukemia treated with imatinib [21].…”

Major response to imatinib and chemotherapy in a newborn patient prenatally diagnosed with generalized infantile myofibromatosis

“…2,3 The recent discovery of a molecular abnormality involving PDGFR-β in pediatric multicentric or familial cases provides a new therapeutic possibility for this disease. [7][8][9] Imatinib is a multikinase inhibitor including PDGFR-β inhibition. A second-line treatment with targeted therapy should be considered only in case of a life-threatening progression of the disease.…”