Driver Genetic Mutations in Spinal Cord Gliomas Direct the Degree of Functional Impairment in Tumor-Associated Spinal Cord Injury

Yoshitaka Nagashima,Toshihiko Wakabayashi,Kosuke Aoki,Fumiharu Ohka,Yotaro Kitano,Masahito Hara,Takahiro Oyama,Hirano Masaki,Kaoru Eguchi,Yusuke Nishimura,Atsushi Natsume,Tomoya Nishii,Hiroshi Ito

doi:10.3390/cells10102525

Yoshitaka Nagashima, Toshihiko Wakabayashi + Show 11 more

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https://doi.org/10.3390/cells10102525

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Abstract

Genetic analysis in glioma has been developed recently. Spinal cord glioma is less common than intracranial glioma. Thus, the clinical significance of genetic mutations in spinal cord gliomas remains unclear. Furthermore, because the spinal cord is an important communication channel between the brain and the rest of the body, increased attention should be paid to its functional prognosis. In this study, we investigated the functional prognosis and driver genetic mutations in eight patients with spinal cord gliomas (World Health Organization grade I, three cases; grade II, two cases; grade III/IV, three cases). IDH mutations were detected in all grade II cases and H3F3A mutations were detected in all grade III/IV cases. The functional status of grade I and II gliomas remained unchanged or improved 1 year after surgery, whereas grade III/IV gliomas remained unchanged or deteriorated. Spinal glioma progenitor cells with H3F3A mutations were associated with accelerated tumor-associated spinal cord injury, which led to functional impairment. Conversely, the presence of IDH mutations, which are rarely reported in spinal gliomas, indicated a relatively favorable functional prognosis.

Highlights

Intramedullary spinal cord gliomas are rarely encountered in central nervous system (CNS) tumors [1,2]; they frequently lead to severe neurological deterioration
We evaluated the relationship between genetic mutations and the degree of deterioration of neurological status in eight patients with spinal cord gliomas
We found three clinical entities divided in terms of the severity of tumor-associated spinal cord injury: World Health Organization (WHO) grade I pilocytic astrocytoma, grade II astrocytoma with isocitrate dehydrogenase (IDH) mutation, and grade III/IV astrocytoma with H3F3A K27M mutation

Summary

Introduction

Intramedullary spinal cord gliomas are rarely encountered in central nervous system (CNS) tumors [1,2]; they frequently lead to severe neurological deterioration. According to a study that analyzed 1033 newly diagnosed spinal glioma cases between 2004 and 2016 based on the National Cancer Database in the United States, World Health Organization (WHO), grade I pilocytic astrocytomas, accounting for 19% of intramedullary spinal gliomas, largely enable maximal safe surgical resection, leading to better outcomes [3]. Given the premium on preserving neurologic function during spinal cord surgery, tumor types play an important role in the degree of spinal cord injury caused by the nature of the tumor and surgical difficulty. Recent genome-level sequencing studies of infratentorial gliomas revealed that discrete tumor types have tumor progenitor cells (i.e., cancer stem cells) with specific genomic driver alterations. Several genetic alterations are thought to play pivotal roles in tumorigenesis

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