Boccia Federica, Barresi Sabina, Vallese Silvia, Martino Valentina Di, Bombaci Sabrina, Massuras Stefania, Gazzin Andrea, Carli Diana, Coppo Paola, Roma Rocco, Giovannoni Isabella, Mussa Alessandro, Alaggio Rita
Department of Medical Sciences, University of Turin, Turin, Italy.
Pathology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Genes Chromosomes Cancer. 2025 Jan;64(1):e70028. doi: 10.1002/gcc.70028.
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.
婴儿肌纤维瘤病（IM）临床表现多样，涵盖从孤立性或多中心性病变到危及生命的全身性病变。IM大多与由PDGFRB基因编码的血小板衍生生长因子受体β（PDGFRβ）酪氨酸激酶的种系或体细胞杂合突变有关。根据临床情况，IM的治疗方法从观察等待到全身化疗不等。靶向治疗，如伊马替尼等酪氨酸激酶抑制剂（TKIs），在治疗具有PDGFRB功能获得性突变的IM病变方面显示出前景。在此，我们报告了两例散发、多灶性且伴有PDGFRB基因融合的IM的首个证据。RNA测序分析揭示了两个分别涉及PDGFRB蛋白激酶结构域与UBE2I和FN1基因的新型融合转录本。虽然基因融合在软组织肿瘤形成中是常见且强效的致癌驱动因素，但此前涉及PDGFRB的融合基因与IM并无关联。基于DNA的二代测序（NGS） panel检测可能无法检测到染色体重排，如易位，这凸显了包括RNA测序在内的全面分子谱分析在诊断和管理患有IM的儿童中的关键作用。
