Spinal cord high-grade infiltrating gliomas in adults: clinico-pathological and molecular evaluation

Alvi, Mohammed Ali; Ida, Cristiane M.; Paolini, Michael A.; Kerezoudis, Panagiotis; Meyer, Jenna; Fritcher, Emily G. Barr; Goncalves, Sandy; Meyer, Frederic B.; Bydon, Mohammed; Raghunathan, Aditya

doi:10.1038/s41379-019-0271-3

Cited by 46 publications

(68 citation statements)

References 38 publications

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“…It has been suggested that TERT promoter mutations are associated with a poor survival rate in IDH-wildtype lower-grade brain gliomas [5,29,36]. The similar effect of TERT promoter mutation in spinal cord glioma was suggested in three cases [2]. In the present study, we revealed that the rate of TERT promoter mutations was 22.4% (13/ 58); additionally, this mutation was found mainly in H3wildtype tumors (9/13), and was associated with a poor prognosis for grade II/III spinal cord gliomas.…”

Section: Discussionmentioning

confidence: 85%

“…Currently, our understating of spinal cord astrocytomas is largely based on advances in their intracranial counterparts, as the low incidence of spinal cord astrocytomas leads to difficulties in collecting sufficient samples to run adequate analyses. However, genetic alterations and the molecular biological profile of spinal cord gliomas seem to be distinct from those of their brain counterparts [1,2,13,27,33,34,37,38].…”

Section: Introductionmentioning

confidence: 99%

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The molecular characteristics of spinal cord gliomas with or without H3 K27M mutation

Chai

Zhang

Liu

et al. 2020

acta neuropathol commun

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Due to the rare incidence of spinal cord astrocytomas, their molecular features remain unclear. Here, we characterized the landscapes of mutations in H3 K27M, isocitrate dehydrogenase 1 (IDH1) R132H, BRAF V600E, and the TERT promoter in 83 diffuse spinal cord astrocytic tumors. Among these samples, thirty-five patients had the H3 K27M mutation; this mutant could be observed in histological grade II (40%), III (40%), and IV (20%) astrocytomas. IDH1 mutations were absent in 58 of 58 cases tested. The BRAF V600E mutation (7/57) was only observed in H3-wildtype astrocytomas, and was associated with a better prognosis in all histological grade II/III astrocytomas. TERT promoter mutations were observed in both H3 K27M-mutant (4/25) and-wildtype (9/33) astrocytomas, and were associated with a poor prognosis in H3-wildtype histological grade II/III astrocytomas. In the 2016 WHO classification of CNS tumors, H3 K27M-mutant diffuse midline gliomas, including spinal cord astrocytomas, are categorized as WHO grade IV. Here, we noticed that the median overall survival of histological grade II/III H3 K27M-mutant cases (n = 28) was significantly longer than that of either the total histological grade IV cases (n = 12) or the H3 K27M-mutant histological grade IV cases (n = 7). We also directly compared H3 K27M-mutant astrocytomas to H3-wildtype astrocytomas of the same histological grade. In histological grade II astrocytomas, compared to H3-wildtype cases (n = 37), H3 K27M-mutant patients (n = 14) had showed a significantly higher Ki-67-positive rate and poorer survival rate. However, no significant differences in these parameters were observed in histological grade III and IV astrocytoma patients. In conclusion, these findings indicate that spinal cord astrocytomas are considerably different from hemispheric and brainstem astrocytomas in terms of their molecular profiles, and that the histological grade cannot be ignored when assessing the prognosis of H3 K27M-mutant spinal cord astrocytomas.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

The molecular characteristics of spinal cord gliomas with or without H3 K27M mutation

Chai

Zhang

Liu

et al. 2020

acta neuropathol commun

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“…In contrast, p.G34R or p.G34V mutation in the H3F3A gene is found in a subset of glioblastomas located in the cerebral hemispheres of adolescents and young adults and is associated with a more favorable prognosis [6,[8][9][10]. While the genetic landscape of supratentorial and brainstem gliomas has now been extensively characterized [9,11], the genetic drivers of spinal cord diffuse gliomas are less understood [1]. Here we report genomic characterization of 13 spinal cord diffuse gliomas that identified recurrent Electronic supplementary material The online version of this article (https ://doi.org/10.1007/s0040 1-019-02072 -2) contains supplementary material, which is available to authorized users.…”

mentioning

confidence: 99%

Recurrent non-canonical histone H3 mutations in spinal cord diffuse gliomas

et al. 2019

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“…All of the reported spinal cord gliomas harboring BRAF V600E mutations are LGGs (Table ) . Among the 24 cases of spinal cord HGGs investigated, none of them harbored BRAF V600E mutation (Table ) . Hence, our case is the first report of a spinal cord HGG harboring BRAF V600E mutation.…”

Section: Discussionmentioning

confidence: 74%

“…3 In comparison, BRAF V600E mutation is rare in intracranial high‐grade gliomas (HGGs), which account for 1.7%–6.3% of cases . In spinal cord gliomas, BRAF alterations including the V600E mutation, copy number gain, and fusion are frequently detected in LGGs, whereas the missense mutation resulting in the substitution of methionine for lysine at residue 27 of the H3 histone family member 3A ( H3F3A K27M) is frequently detected in HGGs . Although several cases of spinal cord LGGs harboring BRAF V600E mutations have been reported, there has been no report of BRAF mutations in spinal cord HGGs.…”

Section: Introductionmentioning

confidence: 99%

Spinal cord anaplastic astrocytoma with BRAF V600E mutation: A case report and review of literature

et al. 2020

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A 17‐year‐old female complained of lower extremity pain that progressed to low back pain accompanied by paraparesis. Magnetic resonance imaging revealed a mass in the conus medullaris of the spinal cord at the thoracic spine 11–12 level. The patient underwent resection of the mass. The pathological diagnosis was anaplastic astrocytoma based on the densely proliferating astrocytic tumor cells without necrosis or microvascular proliferation. The patient received chemoradiotherapy with oral temozolomide and a total of 54 Gy of local irradiation, followed by 24 courses of temozolomide as maintenance chemotherapy. The patient survived for 8 years without tumor recurrence following the initial treatment. Genetic analysis of the tumor revealed a BRAF V600E mutation that has not yet been reported in spinal cord high‐grade gliomas (HGGs). In recent years, the molecular therapy targeting the BRAF V600E mutation has been applied in clinical practice for several cancer types. Although the frequency in spinal cord HGGs is uncertain, it is necessary to investigate BRAF V600E mutation as a potential therapeutic target in the future.

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Spinal cord high-grade infiltrating gliomas in adults: clinico-pathological and molecular evaluation

Cited by 46 publications

References 38 publications

The molecular characteristics of spinal cord gliomas with or without H3 K27M mutation

The molecular characteristics of spinal cord gliomas with or without H3 K27M mutation

Recurrent non-canonical histone H3 mutations in spinal cord diffuse gliomas

Spinal cord anaplastic astrocytoma with BRAF V600E mutation: A case report and review of literature

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