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

Nagashima, Yoshitaka; Nishimura, Yusuke; Ohka, Fumiharu; Eguchi, Kaoru; Ito, Hiroshi; Nishii, Tomoya; Oyama, Tokitaka; Hara, Masahito; Kitano, Yasushi; Hashimoto, Masaki; Wakabayashi, Toshihiko; Natsume, Atsushi

doi:10.3390/cells10102525

Cited by 7 publications

(5 citation statements)

References 31 publications

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“…Nagashima et al, 2021 focused on the impact of Driver Genetic Mutations in Spinal Cord Gliomas and concluded that gliomas with H3F3A mutations were associated with accelerated tumor-associated spinal cord injury, leading to functional impairment. Conversely, the presence of IDH mutations, which are rarely reported in spinal gliomas, indicated a relatively favorable functional prognosis [ 34 ]. Biczok et al, 2021 identified five distinct subgroups in 26 patients (adults and pediatrics) of spinal astrocytomas based on molecular data.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Approaches in Adult Primary Spinal Cord Astrocytoma: A Systematic Review

Anghileri

Broggi

Mazzapicchi

et al. 2022

Cancers

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The issue: Gliomas are primary tumors arising from supporting cells of the central nervous system (CNS), usually in the brain. The 2021 World Health Organization (WHO) classifies gliomas as adult-type diffuse gliomas or circumscribed astrocytic gliomas depending on their histology and molecular features. Spinal astrocytic gliomas are very rare, and nowadays no standard of therapy is available. Treatment options are limited: surgery is often not radical, and adjuvant therapies include mostly radiotherapy (RT) or systemic chemotherapy (CHT). There is lack of knowledge about the efficacy and safety of therapies and their multidisciplinary approaches. The aim of the review: A systematic review of the literature from January 2000 to June 2021 was performed, including both clinical trials and observational studies on histological adult primary spinal cord astrocytomas (SCA), with a minimum follow-up of 6 months and reporting the overall survival, progression-free survival or clinical neurological outcome after any therapeutic approach (surgery, RT or CHT). What are the main findings? A total of 1197 citations were identified by the Medline search and additional records; based on our inclusion criteria, 18 studies were included with a total of 285 adult patients. We documented the lack of any clinical trial. What are the conclusions? The available literature data are limited to series/retrospective studies, including heterogeneous patients, i.e., astrocytoma as well as ependymoma or pediatric/adult age, with scanty data on the outcomes of interest. No clinical trials have been run. Due to the rarity of this disease, multicentric clinical trials with molecular investigations are mandatory to better manage such a rare disease.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Approaches in Adult Primary Spinal Cord Astrocytoma: A Systematic Review

Anghileri

Broggi

Mazzapicchi

et al. 2022

Cancers

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“…In contrast, Nagashima et al. reported R132C and R132H mutations in two patients with Grade 2 intramedullary astrocytomas, noting a favorable prognosis with both patients alive with 22–37 months of follow-up ( 119 ). Next generation sequencing and identification of larger cohorts of IDH -mutant intramedullary astrocytomas is needed to determine its prognostic value.…”

Section: Molecular Landscapementioning

confidence: 98%

Surgical approaches to intramedullary spinal cord astrocytomas in the age of genomics

2022

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Intramedullary astrocytomas represent approximately 30%–40% of all intramedullary tumors and are the most common intramedullary tumor in children. Surgical resection is considered the mainstay of treatment in symptomatic patients with neurological deficits. Gross total resection (GTR) can be difficult to achieve as astrocytomas frequently present as diffuse lesions that infiltrate the cord. Therefore, GTR carries a substantial risk of new post-operative deficits. Consequently, subtotal resection and biopsy are often the only surgical options attempted. A midline or paramedian sulcal myelotomy is frequently used for surgical resection, although a dorsal root entry zone myelotomy can be used for lateral tumors. Intra-operative neuromonitoring using D-wave integrity, somatosensory, and motor evoked potentials is critical to facilitating a safe resection. Adjuvant radiation and chemotherapy, such as temozolomide, are often administered for high-grade recurrent or progressive lesions; however, consensus is lacking on their efficacy. Biopsied tumors can be analyzed for molecular markers that inform clinicians about the tumor’s prognosis and response to conventional as well as targeted therapeutic treatments. Stratification of intramedullary tumors is increasingly based on molecular features and mutational status. The landscape of genetic and epigenetic mutations in intramedullary astrocytomas is not equivalent to their intracranial counterparts, with important difference in frequency and type of mutations. Therefore, dedicated attention is needed to cohorts of patients with intramedullary tumors. Targeted therapeutic agents can be designed and administered to patients based on their mutational status, which may be used in coordination with traditional surgical resection to improve overall survival and functional status.

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“…Isocitrate dehydrogenase (IDH) mutations were first identified in 2008 in intracranial glioblastoma [ 41 ] and in > 80% of WHO grade 2 and 3 cases [ 42 , 43 ]. Because IDH mutations are associated with the prognosis of intracranial gliomas [ 43 , 44 ], IDH mutations are considered clinically significant, and the 2021 WHO classification classifies the common diffuse gliomas of adults into 3 types: “astrocytoma, IDH-mutant”; “oligodendroglioma, IDH-mutant and 1p/19q-codeleted”; and “glioblastoma, IDH-wildtype.” [ 4 ] However, IDH mutations are extremely rare in spinal gliomas and their incidence in spinal cord gliomas is not well understood [ 32 , 45 ] ( Table 1 ). According to the results of immunohistochemistry and Sanger sequencing for 120 midline gliomas, including 35 spinal gliomas, 61 patients tested positive for the H3 K27M mutation, while only 2 cases exhibited the IDH1 R132H mutation [ 46 ].…”

Section: The Clinical Features and Genetic Findings Of Intramedullary...mentioning

confidence: 99%

“…In addition, the remaining 2 cases had translocations at positions 82 (Arg → Lys, R82K) and 76 (Ile → Thr, I76T) of the IDH1 gene, which had never been described in intracranial gliomas in the past. In another study, Takai et al [ 49 ] reported one case of spinal astrocytoma with an IDH1 R132S mutation, and we previously reported 2 cases with IDH1 R132C and IDH1 R132H mutations, respectively [ 45 ]. There is also a report of spinal cord glioma with IDH2 R172 [ 31 ].…”

Section: The Clinical Features and Genetic Findings Of Intramedullary...mentioning

confidence: 99%

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Recent Molecular and Genetic Findings in Intramedullary Spinal Cord Tumors

et al. 2022

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The study of genetic alterations and molecular biology in central nervous system (CNS) tumors has improved the accuracy of estimations of patient prognosis and tumor categorization. Therefore, the updated 2021 World Health Organization (WHO) classification includes various diagnostic genes, molecules, and pathways for diagnosis, as well as histological findings. These findings are expected both to have diagnostic applications and to facilitate new targeted therapies that target tumor-specific genetic changes and molecular biology. Intramedullary spinal cord tumors (IMSCTs) are rare CNS tumors that are difficult to treat because they occur in eloquent areas. Although the genetic underpinnings of IMSCTs remain unclear compared to their intracranial counterparts, the genetic characteristics of these tumors are gradually being revealed. Here, we describe the major changes in the new 2021 WHO classification and review the major types of IMSCTs, with an emphasis on their clinical features and genetic alterations.

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

Cited by 7 publications

References 31 publications

Therapeutic Approaches in Adult Primary Spinal Cord Astrocytoma: A Systematic Review

Therapeutic Approaches in Adult Primary Spinal Cord Astrocytoma: A Systematic Review

Surgical approaches to intramedullary spinal cord astrocytomas in the age of genomics

Recent Molecular and Genetic Findings in Intramedullary Spinal Cord Tumors

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