Recent Molecular and Genetic Findings in Intramedullary Spinal Cord Tumors

Nagashima, Yoshitaka; Nishimura, Yusuke; Eguchi, Kaoru; Yamaguchi, Junya; Haimoto, Shoichi; Ohka, Fumiharu; Takayasu, Misako; Saito, Ryuta

doi:10.14245/ns.2244168.084

Cited by 11 publications

(12 citation statements)

References 68 publications

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“…Recently, distinct cellular origin and prognosis characteristics have been revealed in the H3 K27M‐mutant midline gliomas with different anatomic localization and ages [ 14 , 20 , 21 , 22 , 23 , 24 ]. These findings gradually challenged the current situation that the clinical management of spinal cord diffuse glioma is mainly referred to guidelines of their brain counterparts [ 25 , 26 , 27 ]. However, because of the low incidence and high risk of surgical resection of spinal cord diffuse glioma, controversial results have been reported in different spinal cord astrocytoma studies with small sample sizes [ 16 , 28 , 29 , 30 , 31 ], which cannot provide enough evidence for improving clinical management of spinal glioma.…”

Section: Introductionmentioning

confidence: 99%

Genomic profiling and prognostic factors of H3 K27M‐mutant spinal cord diffuse glioma

Chai

Yan

et al. 2023

Brain Pathology

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H3 K27-altered diffuse midline glioma is a highly lethal pediatric-type tumor without efficacious treatments. Recent findings have highlighted the heterogeneity among diffuse midline gliomas with different locations and ages. Compared to tumors located in the brain stem and thalamus, the molecular and clinicopathological features of H3 K27-altered spinal cord glioma are still largely elusive, thus hindering the accurate management of patients. Here we aimed to characterize the clinicopathological and molecular features of H3 K27M-mutant spinal cord glioma in 77 consecutive cases. We found that the H3 K27M-mutant spinal cord glioma, with a median age of 35 years old, had a significantly better prognosis than H3 K27M-mutant brain tumors. We noticed a molecular heterogeneity of H3 K27M-mutant spinal cord astrocytoma via targeted sequencing with 34 cases. TP53 mutation which occurred in 58.8% of cases is mutually exclusive with PPM1D (26%) and NF1 (44%) mutations. The TP53-mutant cases had a significantly higher number of copy number variants (CNV) and a marginally higher proportion of pediatric patients (age at diagnosis <18 years old, p = 0.056). Cox regression and Kaplan-Meier curve analysis showed that the higher number of CNV events (≥3), chromosome (Chr) 9p deletion, Chr 10p deletion, ATRX mutation, CDK6 amplification, and retinoblastoma protein (RB) pathway alteration are associated with worse survival. Cox regression analysis with clinicopathological features showed that glioblastoma histological type and a high Ki-67 index (>10%) are associated with a worse prognosis. Interestingly, the histological type, an independent prognostic factor in multivariate Cox regression, can also stratify molecular features of H3 K27M-mutant spinal cord glioma, including the RB pathway, KRAS/PI3K pathway, and chromosome arms CNV. In conclusion, although all H3 K27M-mutant spinal cord diffuse glioma were diagnosed as WHO Grade 4, the histological type, molecular features representing chromatin instability, and molecular alterations associated with accelerated cell proliferative activity should not be ignored in clinical management.Rui-Chao Chai and Hao Yan contributed equally to this study.

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Section: Introductionmentioning

confidence: 99%

Genomic profiling and prognostic factors of H3 K27M‐mutant spinal cord diffuse glioma

Chai

Yan

et al. 2023

Brain Pathology

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“…The concordance rate was lower than that in brain/brainstem gliomas [ 7 , 17 ]. Of note, in spite of the low concordance rate, genetic mutations in H3F3A, TP53 , and ATRX , which were hotspot mutations found in spinal cord astrocytoma and were diagnostic and prognostic markers of glioma [ 20 - 22 ], could be detected in CSF-derived ctDNA using next-generation sequencing approach and showed favorable concordance with tissuebased testing. Particularly, H3F3A K27M , the representative diagnostic marker of DMG, was identified in CSF samples of the 2 patients with DMG, suggesting that CSF-based H3F3A K27M testing has the potential to serve as a noninvasive method for the diagnosis of DMG.…”

Section: Discussionmentioning

confidence: 99%

Detection of Glioma-Related Hotspot Mutations Through Sequencing of Cerebrospinal Fluid (CSF)-Derived Circulating Tumor DNA: A Pilot Study on CSF-Based Liquid Biopsy for Primary Spinal Cord Astrocytoma

et al. 2023

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Objective: Although cerebrospinal fluid (CSF)-based liquid biopsy was proved to be practical in molecular analysis of intracranial gliomas, liquid biopsy of primary intramedullary astrocytoma was rarely reported. Given the distinct genomic profiles between primary intramedullary glioma and intracranial astrocytoma, whether the feasibility of CSF-based molecular analysis of intracranial gliomas can be replicated in primary spinal cord astrocytoma needs to be investigated. The aim of this pilot study is to evaluate the feasibility of molecular analysis of primary intramedullary astrocytoma through sequencing CSF-derived circulating tumor DNA (ctDNA).Methods: Two grade IV diffuse midline gliomas, 1 grade II, and 1 grade I astrocytoma were included. Intraoperative collection of peripheral blood and CSF samples was conducted, along with postoperative collection of matched tumor tissues. A panel covering the 1,021 most common driver genes of solid tumors was used for targeted DNA sequencing.Results: CSF-derived ctDNA was detected in 3 CSF samples (2 grade IV diffuse midline gliomas and 1 grade I astrocytoma), 5 mutations were found in both tumor tissues and CSF samples, while 11 mutations and 20 mutations were detected exclusively in tumor tissues and CSF samples, respectively. Importantly, hotspot genetic alterations, including H3F3A K28M, TP53, and ATRX, were identified in CSF and the average mutant allele frequency was often higher in CSF than in tumor tissues.Conclusion: CSF-based liquid biopsy showed potential feasibility for molecular analysis of primary intramedullary astrocytoma through sequencing of ctDNA. This approach may assist in diagnosis and prognostic evaluation of this rare spinal cord tumor.

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“…33 For a sensitive patient population, adjuvant therapies and immunotherapy may represent alternative options. 34,35 However, the role of adjuvant therapies for high-grade intramedullary tumors still needs to be discussed. 36,37 Tumor resection remains the mainstay of spinal cord tumors.…”

Section: Discussionmentioning

confidence: 99%

Clinical Characteristics and Treatment Outcomes of Long-Level Intramedullary Spinal Cord Tumors: A Consecutive Series of 43 Cases

Zhang

Fan

et al. 2023

Neurospine

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Objective: Long-level intramedullary spinal cord tumors (LIMSCTs) cause complex treatment issues. However, LIMSCTs have rarely been analyzed separately. The authors reported a large case series of LIMSCTs and analyzed the clinical characteristics and treatment outcomes.Methods: The medical data of patients with LIMSCTs at our institution between January 2015 and December 2019 were retrospectively reviewed. Demographics, tumor size and location, pathology, extent of resection, and neurological functional status were collected.Results: A total of 43 consecutive cases were included. Twenty-three cases (53.5%) of LIMSCTs were ependymal tumors. All patients with ependymal tumors achieved gross total resection (GTR). In ependymal tumor cases, 3 cases (13%) of ependymal tumors experienced postoperative neurological deterioration, and 66% of them showed an improvement at follow-up; 25.6% were low-grade astrocytic tumors. The rates of GTR, subtotal resection (STR) and partial resection (PR) were 63.6%, 27.3%, and 9.1%, respectively. Twenty-seven percent cases showed postoperative neurological worsening, and 33% of them had an improvement at follow-up; 20.9% were high-grade astrocytic tumors. The excision rates were 44.4% for GTR, 44.4% for STR, and 11% for PR, respectively. Fifty-five percent cases showed postoperative neurological worsening, and none of them had an improvement at follow-up.Conclusion: In this series, all LIMSCTs were gliomas. Aggressive tumor resection did not increase the risk of long-term functional deterioration in ependymal tumors and low-grade astrocytic tumors, but in high-grade astrocytic tumors, patients had a higher risk of neurological deterioration and difficulty in recovery. In ependymal tumors and low-grade astrocytic tumors, patients can achieve long-time survival after performing aggressive tumor resection.

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Recent Molecular and Genetic Findings in Intramedullary Spinal Cord Tumors

Cited by 11 publications

References 68 publications

Genomic profiling and prognostic factors of H3 K27M‐mutant spinal cord diffuse glioma

Genomic profiling and prognostic factors of H3 K27M‐mutant spinal cord diffuse glioma

Detection of Glioma-Related Hotspot Mutations Through Sequencing of Cerebrospinal Fluid (CSF)-Derived Circulating Tumor DNA: A Pilot Study on CSF-Based Liquid Biopsy for Primary Spinal Cord Astrocytoma

Clinical Characteristics and Treatment Outcomes of Long-Level Intramedullary Spinal Cord Tumors: A Consecutive Series of 43 Cases

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