Genomic Landscape of Intramedullary Spinal Cord Gliomas

AbstractIntramedullary spinal cord tumors (IMSCTs) are rare neoplasms that have limited treatment options and are associated with high rates of morbidity and mortality. To better understand the genetic basis of these tumors we performed whole exome sequencing on 45 tumors and matched germline DNA, including twenty-nine spinal cord ependymomas and sixteen astrocytomas. Though recurrent somatic mutations in IMSCTs were rare, we identified NF2 mutations in 15.7% of tumors (ependymoma, N = 7; astrocytoma, N = 1), RP1 mutations in 5.9% of tumors (ependymoma, N = 3), and ESX1 mutations in 5.9% of tumors (ependymoma, N = 3). We further identified copy number amplifications in CTU1 in 25% of myxopapillary ependymomas. Given the paucity of somatic driver mutations, we further performed whole-genome sequencing of 12 tumors (ependymoma, N = 9; astrocytoma, N = 3). Overall, we observed that IMSCTs with intracranial histologic counterparts (e.g. glioblastoma) did not harbor the canonical mutations associated with their intracranial counterparts. Our findings suggest that the origin of IMSCTs may be distinct from tumors arising within other compartments of the central nervous system and provides the framework to begin more biologically based therapeutic strategies.

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Genomic Landscape of Intramedullary Spinal Cord Tumors Suggests Distinct Genetic Origins Compared to Intracranial Histopathologic Counterparts

Neurosurgery ◽

10.1093/neuros/nyz310_332 ◽

2019 ◽

Vol 66 (Supplement_1) ◽

Author(s):

Tej D Azad ◽

Ming Zhang ◽

Rajiv Iyer ◽

Qing Wang ◽

Tomas Garzon-Muvdi ◽

...

Keyword(s):

Spinal Cord ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Treatment Options ◽

Driver Mutations ◽

Whole Genome ◽

Spinal Cord Tumors ◽

Intramedullary Spinal Cord ◽

Molecular Features ◽

The Central Nervous System

Abstract INTRODUCTION Intramedullary spinal cord tumors (IMSCTs) are a rare, heterogeneous group of neoplasms with limited treatment options and high rates of morbidity and mortality. Next-generation sequencing has revealed opportunities for targeted therapies of the intracranial counterparts of IMSCT, but little is known about the molecular features of IMSCT. METHODS To better understand the genetic basis of these tumors we performed whole exome sequencing on fifty-one IMSCT and matched germline DNA, including 29 ependymomas, 16 astrocytomas, 4 gangliogliomas,1hemangioblastoma, and 1 oligodendroglioma. Whole-genome sequencing was further performed on 12 IMSCT to discover possible structural variants. RESULTS Though recurrent somatic mutations in IMSCTs were rare, we identified NF2 mutations in 15.7% of tumors (ependymoma, N = 7; astrocytoma, N = 1), RP1 mutations in 5.9% of tumors (ependymoma, N = 3), and ESX1 mutations in 5.9% of tumors (ependymoma, N = 3). We further identified copy number amplifications in CTU1 in 25% of myxopapillary ependymomas. Given the paucity of somatic driver mutations, we further performed whole-genome sequencing of 12 tumors (ependymoma, N = 9; astrocytoma, N = 3). Overall, we observed that IMSCTs with intracranial histologic counterparts did not harbor the canonical mutations associated with their intracranial counterparts (eg glioblastoma). CONCLUSION Our findings suggest that the origin of IMSCTs may be distinct from tumors arising within other compartments of the central nervous system and provides a framework to begin more biologically based therapeutic strategies.

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Nonenhancing tumors of the spinal cord

Journal of Neurosurgery Spine ◽

10.3171/spi-07/09/10/403 ◽

2007 ◽

Vol 7 (4) ◽

pp. 403-407 ◽

Cited By ~ 20

Author(s):

J. Bradley White ◽

Gary M. Miller ◽

Kennith F. Layton ◽

William E. Krauss

Keyword(s):

Spinal Cord ◽

Common Finding ◽

Subtotal Resection ◽

Low Grade ◽

Spinal Cord Tumors ◽

Intramedullary Tumors ◽

Intramedullary Spinal Cord ◽

Tumor Invasiveness ◽

The Central Nervous System ◽

Tumor Types

Object Enhancement of pathological entities in the central nervous system is a common finding when the blood–brain barrier has been compromised. In the brain, the presence or absence of gadolinium enhancement is often an indicator of tumor invasiveness and/or grade. In the spinal cord, however, contrast enhancement has been shown in all tumor types, regardless of grade. In this study the authors explore the incidence of nonenhancing tumors of the spinal cord and the clinical course of patients with these lesions. Methods A retrospective analysis was conducted in which investigators examined the patterns of enhancement of histologically proven intramedullary spinal cord tumors that had been evaluated at the Mayo Clinic between 1998 and 2002. The tumors that did not enhance were the subject of this report. Results A total of 130 patients with intramedullary tumors were evaluated. Of those, 11 patients (9%) had tumors that did not enhance. Histologically, a majority of tumors were astrocytomas (eight low-grade and two high-grade lesions); one tumor was a subependymoma. Morphologically, most of the tumors were diffuse and none had associated cysts. Tumors spanned from two to seven levels and were located throughout the spinal cord (four cervical, three cervicothoracic, one thoracic, and three thoracolumbar). Biopsy procedures were performed in eight patients, subtotal resection was performed in two, and gross-total resection in one. After a mean follow-up period of 19 months, tumors remained stable in eight patients but progressed in three, two of whom died. Conclusions A number of intramedullary spinal cord tumors will not enhance after addition of contrast agents. The absence of enhancement does not imply the absence of tumor.

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Intramedullary spinal cord tumors: a review of current and future treatment strategies

Neurosurgical FOCUS ◽

10.3171/2015.5.focus15158 ◽

2015 ◽

Vol 39 (2) ◽

pp. E14 ◽

Cited By ~ 57

Author(s):

Matthew K. Tobin ◽

Joseph R. Geraghty ◽

Herbert H. Engelhard ◽

Andreas A. Linninger ◽

Ankit I. Mehta

Keyword(s):

Spinal Cord ◽

Treatment Options ◽

Treatment Strategies ◽

Incidence Rates ◽

Subtotal Resection ◽

Spinal Cord Tumors ◽

Intramedullary Spinal Cord ◽

Low Incidence ◽

New Research ◽

Localized Drug Delivery

Intramedullary spinal cord tumors have low incidence rates but are associated with difficult treatment options. The majority of patients with these tumors can be initially treated with an attempted resection. Unfortunately, those patients who cannot undergo gross-total resection or have subtotal resection are left with few treatment options, such as radiotherapy and chemotherapy. These adjuvant treatments, however, are associated with the potential for significant adverse side effects and still leave patients with a poor prognosis. To successfully manage these patients and improve both their quality of life and prognosis, novel treatment options must be developed to supplement subtotal resection. New research is underway investigating alternative therapeutic approaches for these patients, including directed, localized drug delivery and nanomedicine techniques. These and other future investigations will hopefully lead to promising new therapies for these devastating diseases.

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