Novel PDGFRB Gene Fusions in Two Cases of Infantile Myofibromatosis

Abstract

Infantile myofibromatosis (IM) comprises a wide clinical spectrum, ranging from solitary or multicentric lesions to generalized life-threatening forms. IM is mostly linked to germline or somatic heterozygous mutations in the PDGFRβ tyrosine kinase, encoded by the PDGFRB gene. Treatments for IM range from wait and see approach to systemic chemotherapy, according to the clinical context. Targeted therapies, such as tyrosine kinase inhibitors (TKIs) like Imatinib, show promise in treating IM lesions with PDGFRB gain-of-function mutations. Here, we report the first evidence of two sporadic, multifocal IM with PDGFRB gene fusions. RNA sequencing analysis revealed two novel fusion transcripts involving the protein kinase domain of PDGFRB, with UBE2I and FN1 genes, respectively. Although gene fusions are frequent and potent oncogenic drivers in soft-tissue neoplasia, fusion genes involving PDGFRB have not previously been linked to IM. DNA-based NGS panel testing may not detect chromosomal rearrangements, such as translocations, emphasizing the critical role of comprehensive molecular profiling, including RNA sequencing, in diagnosing and managing children with IM.