Case report: Novel NIPBL-BEND2 fusion gene identified in osteoblastoma-like phosphaturic mesenchymal tumor of the fibula

Tomohisa Sakai; Yusuke Okuno; Norihiro Murakami; Yoshie Shimoyama; Shiro Imagama; Yoshihiro Nishida

doi:10.3389/fonc.2022.956472

Case report: Novel NIPBL-BEND2 fusion gene identified in osteoblastoma-like phosphaturic mesenchymal tumor of the fibula

Front Oncol. 2023 Jan 5:12:956472. doi: 10.3389/fonc.2022.956472. eCollection 2022.

Authors

Tomohisa Sakai^{1

2}, Yusuke Okuno³, Norihiro Murakami⁴, Yoshie Shimoyama⁵, Shiro Imagama¹, Yoshihiro Nishida^{1

2

6}

Affiliations

¹ Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
² Rare Cancer Center, Nagoya University Hospital, Nagoya, Japan.
³ Department of Virology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
⁴ Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁵ Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.
⁶ Department of Rehabilitation, Nagoya University Hospital, Nagoya, Japan.

Abstract

Phosphaturic mesenchymal tumor (PMT) is a rare tumor that secretes fibroblast growth factor 23 (FGF23) and causes hypophosphatemia and tumor-induced osteomalacia (TIO). Fusion genes FN1-FGFR1 and FN1-FGF1 have been detected in some PMTs, but the pathogenesis of PMTs without these fusion genes remains unclear. Here, we report a 12-year-old boy with persistent muscle weakness and gait disturbance. Roentgenographic examination revealed a radiolucent lesion with endosteal scalloping in the left fibula, while his serum level of FGF23 was markedly increased. Combined with simple X-ray findings of other body parts, we suspected that TIO was caused by PMT, and resected the tumor. After resection, the serum level of FGF23 started to decrease immediately and normalized within 3 hours after resection, with this being earlier than normalization of the serum phosphorus level. In RNA sequencing, FN1-FGFR1 and FN1-FGF1 were not detected, but a novel NIPBL-BEND2 fusion gene was identified. When we forcedly expressed this fusion gene in HEK293T cells and MG63 cells, cell proliferation was enhanced in both cell lines. Furthermore, Gene set enrichment analysis of HEK293T cells showed significant upregulation of MYC-target genes. Our results suggest that this novel NIPBL-BEND2 fusion gene promotes cell proliferation possibly via the MYC pathway and might be one of the etiologies of PMTs other than FN1-FGFR1 or FN1-FGF1.

Keywords: RNA sequencing; bone tumor; fusion gene; phosphaturic mesenchymal tumor; tumor induced osteomalacia; whole exome sequencing.

Publication types

Case Reports