Molecular characterization reveals NF1 deletions and FGFR1-activating mutations in a pediatric spinal oligodendroglioma

Abstract

Pediatric spinal oligodendrogliomas are rare and aggressive tumors. They do not share the same molecular features of adult oligodendroglioma, and no previous reports have examined the molecular features of pediatric spinal oligodendroglioma. We present the case of a child with a recurrent spinal anaplastic oligodendroglioma. We performed whole exome (paired tumor and germline DNA) and transcriptome (tumor RNA) sequencing, which revealed somatic mutations in NF1 and FGFR1. These data allowed us to explore potential personalized therapies for this patient and expose molecular drivers that may be involved in similar cases.

Keywords: NF1; anaplastic oligodendroglioma; fibroblast growth factor receptor type 1; molecular sequence data; precision medicine; spinal cord neoplasms.

FIGURE 1

Spinal oligodendroglioma imaging and pathology. (A) Spinal MRI, sagittal image, T1 series postcontrast, illustrating tumor after initial resection. (B) Spinal MRI, sagittal image, T1 series post-contrast, showing recurrent disease in the cervical spine, primarily in the C4-T2 region. (C) Tumor parenchyma shows histologic findings on hematoxylin and eosin stain consistent with grade III anaplastic oligodendroglioma: focal high density of round to spindled cells; many cells with perinuclear halos; scattered dark and angulated anaplastic nuclei; two large areas of microvascular proliferation at the left side of the figure; and microcysts filled with mucin are prominent near the lower right corner of the figure. (D) Alpha thalassemia/mental retardation syndrome X-linked (ATRX) protein is preserved in nuclei of vascular cells and neoplastic cells (ATRX loss is frequently seen in ATRX-mutated astrocytoma).

FIGURE 2

Proposed targeted inhibitors of the Ras-MAPK pathway. Neurofibromin loss-of-function and FGFR1 activation in this tumor are the two identified potential drivers of oncogenesis, and inhibitors of either pathway are attractive targeted therapy agents. Upstream inhibition of the Ras-MAPK pathway at the level of FGFR1 can be achieved with the tyrosine kinase inhibitor, ponatinib. Downstream inhibition of the Ras-MAPK pathway can be achieved with the MEK inhibitor, trametinib.