Myxoid glioneuronal tumor of the septum pellucidum and lateral ventricle is defined by a recurrent PDGFRA p.K385 mutation and DNT-like methylation profile

Solomon, David A.; Korshunov, Andrey; Sill, Martin; Jones, David; Kool, Marcel; Pfister, Stefan M.; Fan, Xuemo; Bannykh, Serguei; Hu, Jethro; Danielpour, Moise; Li, Rong; Johnston, James M.; Cham, Elaine; Cooney, Tabitha; Sun, Peter; Bush, Nancy Ann Oberheim; McDermott, Michael W.; Ziffle, Jessica Van; Onodera, Courtney; Grenert, James P.; Bastian, Boris C.; Villanueva-Meyer, Javier; Pekmezci, Melike; Bollen, Andrew W.; Perry, Arie

doi:10.1007/s00401-018-1883-2

Cited by 42 publications

(43 citation statements)

References 16 publications

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“…PDGFRα mutations have been reported in low grade glioneuronal tumors of the septum pellucidum [204], despite more typically being associated with HGG in the context of other mutations [109,193,207,226,227]. The clinical implications of these rare alterations are not yet fully understood.…”

Section: Other Rare Ras/mapk Alterationsmentioning

confidence: 99%

Pediatric low-grade glioma in the era of molecular diagnostics

Ryall

Tabori

Hawkins

2020

acta neuropathol commun

206

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: Other Rare Ras/mapk Alterationsmentioning

confidence: 99%

Pediatric low-grade glioma in the era of molecular diagnostics

Ryall

Tabori

Hawkins

2020

acta neuropathol commun

206

251

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“…A graphical summary of the evolution of the field within the context of brain tumours is displayed in Figure . DNA methylation is further gaining importance for tumour entity definition and is increasingly being used for the allocation of rare cancers into either known tumour classes or the identification of new entities , a collection of which are summarized in Figure .…”

Section: Dna Methylation In Cancermentioning

confidence: 99%

“…Myxoid glioneuronal tumour is a low‐grade glioneuronal neoplasm of the septum pellucidum, the lateral ventricle, the corpus callosum or the periventricular white matter with DNT‐like or RGNT‐like histological features that is defined by recurrent PDGFRA p.K385 mutations . DNA methylation patterns seem to be close to DNT .…”

Section: New or Emerging Paediatric Tumour Classes Identified By Dna mentioning

confidence: 99%

Invited Review: DNA methylation‐based classification of paediatric brain tumours

Perez

Capper

2020

Neuropathology Appl Neurobio

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2020) Neuropathology and Applied Neurobiology 46, 28-47 DNA methylation-based classification of paediatric brain tumours DNA methylation-based machine learning algorithms represent powerful diagnostic tools that are currently emerging for several fields of tumour classification. For various reasons, paediatric brain tumours have been the main driving forces behind this rapid development and brain tumour classification tools are likely further advanced than in any other field of cancer diagnostics. In this review, we will discuss the main characteristics that were important for this rapid advance, namely the high clinical need for improvement of paediatric brain tumour diagnostics, the robustness of methylated DNA and the consequential possibility to generate high-quality molecular data from archival formalin-fixed paraffin-embedded pathology specimens, the implementation of a single array platform by most laboratories allowing data exchange and data pooling to an unprecedented extent, as well as the high suitability of the data format for machine learning. We will further discuss the four most central output qualities of DNA methylation profiling in a diagnostic setting (tumour classification, tumour sub-classification, copy number analysis and guidance for additional molecular testing) individually for the most frequent types of paediatric brain tumours. Lastly, we will discuss DNA methylation profiling as a tool for the detection of new paediatric brain tumour classes and will give an overview of the rapidly growing family of new tumours identified with the aid of this technique.

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“…Eight patients with low-grade glioneuronal tumors harboring the defining PDGFRA p.K385I or p.K385L dinucleotide substitution by targeted next-generation sequencing analysis were included in this study. Patients MGNT #1-4 have previously been reported in part (27). All tumor specimens were fixed in 10% neutral-buffered formalin and embedded in paraffin.…”

Section: Patient Cohort and Tumor Samplesmentioning

confidence: 99%

“…"Myxoid glioneuronal tumor, PDGFRA p.K385-mutant" is a recently described tumor entity of the central nervous system (CNS) that has a stereotypic location in the septum pellucidum and a characteristic dinucleotide mutation at codon 385 of the PDGFRA oncogene replacing lysine with either leucine or isoleucine (p.K385L/I) in the encoded platelet-derived growth factor receptor alpha protein (27). These tumors are low-grade glioneuronal neoplasms with histologic features reminiscent of either dysembryoplastic neuroepithelial tumor (DNT) or rosette-forming glioneuronal tumor (RGNT), composed of oligodendrocyte-like cells in a prominent myxoid stroma.…”

Section: Introductionmentioning

confidence: 99%

Myxoid glioneuronal tumor, PDGFRA p.K385‐mutant: clinical, radiologic, and histopathologic features

et al. 2019

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Myxoid glioneuronal tumor, PDGFRA p.K385-mutant" is a recently described tumor entity of the central nervous system with a predilection for origin in the septum pellucidum and a defining dinucleotide mutation at codon 385 of the PDGFRA oncogene replacing lysine with either leucine or isoleucine (p.K385L/I). Clinical outcomes and optimal treatment for this new tumor entity have yet to be defined. Here, we report a comprehensive clinical, radiologic, and histopathologic assessment of eight cases. In addition to its stereotypic location in the septum pellucidum, we identify that this tumor can also occur in the corpus callosum and periventricular white matter of the lateral ventricle. Tumors centered in the septum pellucidum uniformly were associated with obstructive hydrocephalus, whereas tumors centered in the corpus callosum and periventricular white matter did not demonstrate hydrocephalus. While multiple patients were found to have ventricular dissemination or local recurrence/progression, all patients in this series remain alive at last clinical follow-up despite only biopsy or subtotal resection without adjuvant therapy in most cases. Our study further supports "myxoid glioneuronal tumor, PDGFRA p.K385mutant" as a distinct CNS tumor entity and expands the spectrum of clinicopathologic and radiologic features of this neoplasm.

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Myxoid glioneuronal tumor of the septum pellucidum and lateral ventricle is defined by a recurrent PDGFRA p.K385 mutation and DNT-like methylation profile

Cited by 42 publications

References 16 publications

Pediatric low-grade glioma in the era of molecular diagnostics

Pediatric low-grade glioma in the era of molecular diagnostics

Invited Review: DNA methylation‐based classification of paediatric brain tumours

Myxoid glioneuronal tumor, PDGFRA p.K385‐mutant: clinical, radiologic, and histopathologic features

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