Diffuse high-grade gliomas with H3 K27M mutations carry a dismal prognosis independent of tumor location

Karremann, Michael; Gielen, Gerrit H.; Hoffmann, Marion; Wiese, Maria; Colditz, Niclas; Warmuth‐Metz, Monika; Bison, Brigitte; Claviez, Alexander; Vuurden, D.G. van; Bueren, André O. von; Gessi, Marco; Kühnle, Ingrid; Hans, Volkmar; Benesch, Martin; Sturm, Dominik; Kortmann, Rolf‐Dieter; Waha, Andreas; Pietsch, Torsten; Kramm, Christof M.

doi:10.1093/neuonc/nox149

Cited by 220 publications

(205 citation statements)

References 39 publications

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“…Diffuse midline gliomas represent a subset of pediatric gliomas that have significantly poor survival rates and are clinically aggressive regardless of their anatomical location [26, 23]. These types of tumors are described as having a predominately astrocytic lineage with mutations affecting K27M in either H3F3A or HIST1H3B/C that encode for histone 3, and have been implicated in driving gliomagenesis [26].…”

Section: Discussionmentioning

confidence: 99%

“…These types of tumors are described as having a predominately astrocytic lineage with mutations affecting K27M in either H3F3A or HIST1H3B/C that encode for histone 3, and have been implicated in driving gliomagenesis [26]. Neoplasms with these types of mutations primarily affect children and adolescents.…”

Section: Discussionmentioning

confidence: 99%

“…Neoplasms with these types of mutations primarily affect children and adolescents. In a recent study by Karreman et al [26], 85 diffuse midline gliomas were studied and overall survival was predicted based on variants of the H3 K27M mutation. The authors of that study found that the H3 K27M variants were the only factor associated with worse prognosis compared to the wild-type allele ( p = 0.009).…”

Section: Discussionmentioning

confidence: 99%

“…Neoplastic location and histological grade were not associated with any significant influence on overall survival in their cohort. Other studies have also shown dismal survival outcomes even with radiotherapy and surgery in cohorts expressing the H3 K27M mutations compared to wild-type tumors [26-29]. With treatment options for this type of histologically unique neoplasm lacking, more needs to be done to better understand their pathology and outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…With treatment options for this type of histologically unique neoplasm lacking, more needs to be done to better understand their pathology and outcomes. At present, surgery does not seem to improve outcomes in patients with gliomas featuring the K27M mutation even though it is the standard of care in the treatment of most accessible pediatric brain neoplasms [26, 30]. …”

Section: Discussionmentioning

confidence: 99%

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Pediatric Brainstem Gliomas: A Retrospective Study of 180 Patients from the SEER Database

et al. 2019

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Background/Aims: Large population-based studies are needed to assess the epidemiology and survival risk factors associated with pediatric brainstem gliomas. This retrospective study explores factors that may influence survival in this population. Methods: Utilizing the SEER database, the authors retrospectively assessed survival in histologically confirmed brainstem gliomas in patients aged 17 and younger. Survival was described with Kaplan-Meyer curves and multivariate regression analysis. Results: This analysis of 180 cases showed that age (hazard ratio [HR] 1.04, 95% CI 0.96–1.14, p = 0.34), non-white race (HR 1.00, 95% CI 0.35–2.85 p > 0.99), distant or invasive extension of the tumor (HR 0.4, 95% CI 0.08–2.53, p = 0.37), and radiation therapy (HR 1.27, 95% CI 0.52–3.11, p = 0.61) were not associated with decreased survival. High-grade tumor status (HR 8.64, 95% CI 3.49–21.41, p < 0.001) was associated with decreased survival. Partial resection (HR 0.11, 95% CI 0.04–0.30, p < 0.001) and gross-total resection (HR 0.03, 95% CI 0.01–0.14, p < 0.001) were associated with improved survival. Conclusions: High-grade brainstem gliomas have a worse prognosis. Early diagnosis and surgery appear to be associated with improved survival, while the role of radiation is unclear.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Pediatric Brainstem Gliomas: A Retrospective Study of 180 Patients from the SEER Database

et al. 2019

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A Case of Progressive Myelopathy in a Middle-aged Woman

2019

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A 48-year-old woman presented to the emergency department with a 2-month history of progressive lower extremity weakness, sensory loss, and sphincter dysfunction. In the weeks prior to onset, she traveled to Yosemite National Park but denied any particular infectious exposures or symptoms including rash. She reported no personal or family medical history. Although she did consume a variety of nutraceuticals, she denied medication and recreational drug use.On examination, mental status, cranial nerves, and upper extremities were normal. Lower extremities were significant for her right side having greater pyramidal weakness than the left, with brisk reflexes and right ankle clonus, as well as a sensory level to pinprick at T6. Magnetic resonance imaging (MRI) of the total spine with and without gadolinium is seen in Figure 1. Initial investigations were notable for normal complete blood cell count, electrolytes, kidney and liver function, B 12 , and thyrotropin as well as an unremarkable MRI of the brain. Three lumbar punctures were performed over the course of the patient's hospitalization, each with a white blood cell count less than 5 /μL (to convert to ×10 9 /L, multiply by 0.001), normal IgG index, absent oligoclonal bands, normal protein and glucose levels, and benign cytology. A comprehensive infectious and inflammatory workup including HIV, herpes simplex virus, varicella-zoster virus, Lyme disease, antinuclear antibodies, astrocyte aquaporin-4 autoantibody, myelin oligodendrocyte glycoprotein autoantibody, and serum and cerebrospinal fluid autoimmune panels were negative. Whole-body positron emission tomography demonstrated hypermetabolism of the midthoracic cord.

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Clinicopathological characteristics and survival of spinal cord astrocytomas

et al. 2020

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Diffuse high-grade gliomas with H3 K27M mutations carry a dismal prognosis independent of tumor location

Abstract: These results substantiate the clinical significance of considering diffuse midline glioma, H3 K27M-mutant, as a distinct entity corresponding to WHO grade IV, carrying a universally fatal prognosis.

Cited by 220 publications

References 39 publications

Pediatric Brainstem Gliomas: A Retrospective Study of 180 Patients from the SEER Database

Pediatric Brainstem Gliomas: A Retrospective Study of 180 Patients from the SEER Database

A Case of Progressive Myelopathy in a Middle-aged Woman

Clinicopathological characteristics and survival of spinal cord astrocytomas

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