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  • Review Article
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Spinal cord tumours: advances in genetics and their implications for treatment

Nature Reviews Neurology volume 9, pages 257–266 (2013)Cite this article

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Abstract

Tumours of the spinal cord, although rare, are associated with high morbidity. Surgical resection remains the primary treatment for patients with this disease, and offers the best chance for cure. Such surgical procedures, however, carry substantial risks such as worsening of neurological deficit, paralysis and death. New therapeutic avenues for spinal cord tumours are needed, but genetic studies of the molecular mechanisms governing tumourigenesis in the spinal cord are limited by the scarcity of high-quality human tumour samples. Many spinal cord tumours have intracranial counterparts that have been extensively studied, but emerging data show that the tumours are genetically and biologically distinct. The differences between brain and spine tumours make extrapolation of data from one to the other difficult. In this Review, we describe the demographics, genetics and current treatment approaches for the most commonly encountered spinal cord tumours—namely, ependymomas, astrocytomas, haemangioblastomas and meningiomas. We highlight advances in understanding of the biological basis of these lesions, and explain how the latest progress in genetics and beyond are being translated to improve patient care.

Key Points

  • Familial neurofibromatosis type 1 is associated with spinal astrocytoma and neurofibromas, whereas familial neurofibromatosis type 2 (NF2) is associated with spinal ependymoma and meningioma

  • von Hippel–Lindau (VHL) disease and mutations in the VHL gene are associated with spinal haemangioblastoma

  • Mutations in the gene encoding the histone 3 variant H3.3 (H3F3A) and in the fusion gene BRAF–KIAA1549 are evident in spinal astrocytomas

  • The genes associated with ependymoma (including mutations in NF2, HOXB5 and PLAG2) are heterogeneous, varying according to histological subtype, tumour location and patient age

  • Genes encoding protein 4.1 family members NF2 and DAL-1, members of the Hedgehog signalling pathway, matrix metalloproteinase-9, and tissue inhibitors of metalloproteinases, have been implicated in meningioma

  • Surgical resection and adjuvant radiotherapy remain the primary treatment modalities for spinal cord tumours, and targeted therapeutics are under investigation

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Figure 1: Surgery and imaging in spinal cord astrocytoma.
Figure 2: Surgery and imaging in spinal cord ependymoma.
Figure 3: Surgical and preoperative imaging of haemangioblastoma in the cervical spine.
Figure 4: Surgery and imaging of spinal cord meningioma.

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Acknowledgements

This work was funded in part by the Burroughs Wellcome Career Award for Medical Scientists and the Johns Hopkins Clinician Scientist Award. Z. L. Gokaslan receives instructorship and research support from AO North America, AO Spine, American Association of Neurological Surgeons Neurosurgery Research and Education Foundation, and the Orthopaedic Research Foundation.

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  1. Department of Neurosurgery, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, 21287, MD, USA

    Patricia L. Zadnik, Ziya L. Gokaslan & Chetan Bettegowda

  2. Department of Pathology, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, 21287, MD, USA

    Peter C. Burger

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P. L. Zadnik and C. Bettegowda researched data for the article. All authors provided substantial contributions to discussions of the content, writing the article, and to reviewing and/or editing the manuscript before submission.

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Correspondence to Chetan Bettegowda.

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Competing interests

Z. L. Gokaslan is a stock shareholder in US Spine and Spinal Kinetics. The other authors declare no competing interests.

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Zadnik, P., Gokaslan, Z., Burger, P. et al. Spinal cord tumours: advances in genetics and their implications for treatment. Nat Rev Neurol 9, 257–266 (2013). https://doi.org/10.1038/nrneurol.2013.48

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