H3 K27M Mutation in Gangliogliomas can be Associated with Poor Prognosis

Kleinschmidt-DeMasters, B. K.; Donson, Andrew M.; Foreman, Nicholas K.; Dorris, Kathleen

doi:10.1111/bpa.12455

Cited by 36 publications

(24 citation statements)

References 16 publications

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“…H3.3 p.K27M is exclusively observed in tumors arising in the midline, including the pons, diencephalon/thalamus and spinal cord [66,109,134,193,207,226,227]. Although more frequent in HGG, H3.3 p.K27M has been reported in pLGG including pilocytic astrocytoma [82,153], ganglioglioma [102,112,158] and diffuse astrocytoma [187,205]. In one series of pediatric thalamic glioma, H3.3 p.K27M was noted in 12% of low grade cases [187].…”

Section: H3f3a Mutationsmentioning

confidence: 99%

“…In one series of pediatric thalamic glioma, H3.3 p.K27M was noted in 12% of low grade cases [187]. Interestingly, H3.3 p.K27M has been shown to co-occur with additional hotspot mutations, including BRAF p.V600E, FGFR1 p.N546K or p.K656E, and NF1 mutations [102,112,158,187]. Patients with H3.3 p.K27M pLGG have the potential to live longer than patients with H3.3 p.K27M glioma with high grade histologic features.…”

Section: H3f3a Mutationsmentioning

confidence: 99%

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Pediatric low-grade glioma in the era of molecular diagnostics

Ryall

Tabori

Hawkins

2020

acta neuropathol commun

236

251

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Low grade gliomas are the most frequent brain tumors in children and encompass a spectrum of histologic entities which are currently assigned World Health Organisation grades I and II. They differ substantially from their adult counterparts in both their underlying genetic alterations and in the infrequency with which they transform to higher grade tumors. Nonetheless, children with low grade glioma are a therapeutic challenge due to the heterogeneity in their clinical behaviorin particular, those with incomplete surgical resection often suffer repeat progressions with resultant morbidity and, in some cases, mortality. The identification of up-regulation of the RAS-mitogen-activated protein kinase (RAS/MAPK) pathway as a near universal feature of these tumors has led to the development of targeted therapeutics aimed at improving responses while mitigating patient morbidity. Here, we review how molecular information can help to further define the entities which fall under the umbrella of pediatric-type low-grade glioma. In doing so we discuss the specific molecular drivers of pediatric low grade glioma and how to effectively test for them, review the newest therapeutic agents and their utility in treating this disease, and propose a risk-based stratification system that considers both clinical and molecular parameters to aid clinicians in making treatment decisions.

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Section: H3f3a Mutationsmentioning

confidence: 99%

Section: H3f3a Mutationsmentioning

confidence: 99%

Pediatric low-grade glioma in the era of molecular diagnostics

Ryall

Tabori

Hawkins

2020

acta neuropathol commun

236

251

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“…Since then, an increasing number of cases with pure pilocytic astrocytoma (PA) or ganglioglioma (GG) morphology have been published [ 9 , 10 , 11 , 12 , 13 , 14 ], including from our own group [ 15 ]. Indeed, in a report on 18 patients with anaplastic GGs (13 adults; 5 children), H3 K27M mutation was found in 17% of cases, and thus anaplastic GGs appear particularly likely to show this mutation [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

H3 K27M-mutant gliomas in adults vs. children share similar histological features and adverse prognosis

Kleinschmidt‐DeMasters¹,

Levy²

2018

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Background: H3 K27M mutation was originally described in pediatric diffuse intrinsic pontine gliomas (DIPGs), but has been recently recognized to occur also in adult midline diffuse gliomas, as well as midline tumors with other morphologies, including gangliogliomas (GGs), anaplastic GGs, pilocytic astrocytomas (PAs), and posterior fossa ependymomas. In a few patients with H3 K27M-mutant tumors with these alternate morphologies, longer survival has been reported, making grading difficult for the neuropathologist. Few series compare tumors in adult vs. pediatric cohorts; we report our 4-year experience. Materials and methods: Text Word database searches using “H3 K27M” in reports generated between January 2013 and November 10, 2017 were used to identify patients. Clinical and histological features as well as survival were evaluated for each case. Results: 28 H3 K27M-mutant tumors were identified, with equal numbers of adults (13) vs. children (15). For adults, mean and median age was 52 years (range = 27 – 81 years), 2 decades older than a recently-published adult series. Tumors involved thalamic (adult = 7; pediatric = 7), spinal cord (adult = 4; pediatric = 2), pons (adult = 1; pediatric = 6), and hypothalamic (n = 1) sites. Other morphologies at presentation included pure GG (n = 3, pediatric) and PA (n = 1, adult). One adult and 1 pediatric patient each presented with leptomeningeal dissemination or developed leptomeningeal dissemination within 1 year after diagnosis, with transformation from PA or GG histology to glioblastoma. Mean survival was 9.3 (adults) vs. 8.9 (pediatric) months. Patients with tumors of other morphologies (GG, PA) did not enjoy extended survival. Conclusion: H3 K27M-mutant tumors can affect patients at advanced ages, may show leptomeningeal dissemination at time of presentation, and “pure” GG or PA morphology is not rare. Regardless of patient age or tumor morphology, patients fare equally poorly.

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“…They mainly occur in midline structures, such as the pons and thalamus of children and young adults, and are highly infiltrative [2]. More recently, case reports have described the H3K27M mutation in circumscribed (non-diffuse) gliomas, many of which are low-grade (e.g., pilocytic astrocytoma, ganglioglioma) [1, 3–5] (additional references are provided in Online Resource 1). Because of the rarity of these tumors, it is unknown whether they carry the poor clinical outcome ascribed to H3K27M-mutant infiltrating gliomas of the midline.…”

mentioning

confidence: 99%