Comprehensive analysis of diverse low-grade neuroepithelial tumors with FGFR1 alterations reveals a distinct molecular signature of rosette-forming glioneuronal tumor

Lucas, C.H.; Gupta, Rohit; Doo, Pamela; Lee, Julieann C.; Cadwell, Cathryn R.; Ramani, Biswarathan; Hofmann, J; Sloan, Emily A.; Kleinschmidt‐DeMasters, Bette K.; Lee, Han S.; Wood, Matthew D.; Grafe, Marjorie R.; Born, Donald E.; Vogel, Hannes; Salamat, Shahriar; Puccetti, Diane; Scharnhorst, David; Samuel, David; Cooney, Tabitha; Cham, Elaine; Jin, Lee Way; Khatib, Ziad; Maher, Ossama M.; Chamyan, Gabriel; Brathwaite, Carole; Bannykh, Serguei; Mueller, Sabine; Kline, Cassie; Banerjee, Anu; Reddy, Alyssa; Taylor, Jennie; Clarke, Jennifer; Bush, Nancy Ann Oberheim; Butowski, Nicholas; Gupta, Nalin; Auguste, Kurtis I.; Sun, Peter; Roland, Jarod L.; Raffel, Corey; Aghi, Manish K.; Theodosopoulos, Philip V.; Chang, Edward F.; Hervey-Jumper, Shawn L.; Phillips, Joanna J.; Pekmezci, Melike; Bollen, Andrew W.; Tihan, Tarık; Chang, Susan M.; Berger, Mitchel S.; Perry, Arie; Solomon, David A.

doi:10.1186/s40478-020-01027-z

Cited by 40 publications

(53 citation statements)

References 44 publications

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“…Despite its nomenclature, multiple cases of focal, circumscribed parenchymal tumor have resolved to diffuse leptomeningeal glioneuronal tumor on methylome analysis [ 90 ], making the classification of this entity unclear. Epigenetic analysis is further aiding the delineation of rosette-forming glioneuronal tumor from PA and other low grade neuroepithelial tumors with overlapping genomic signatures, with recent description of FGFR1 p.N546 or p.K656 mutation with PIK3CA or PIK3R1 appearing to represent a molecular signature specific to rosette-forming glioneuronal tumor [ 42 ].…”

Section: High Risk Features Of Pamentioning

confidence: 99%

Adult pilocytic astrocytoma in the molecular era: a comprehensive review

et al. 2021

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Adult pilocytic astrocytoma (PA) is less prevalent than pediatric PA and is associated with a worse prognosis. In a literature review, we found that 88.3% of the molecular alterations in adult PA are associated with MAPK pathway dysregulation. The most common alterations are fusions of BRAF. Understanding of the mechanisms underlying this pathway has evolved substantially, heralding advancements in specific targeted therapy. Here, we review clinical and molecular features of adult PA, characteristics predicting aggressive behavior and approaches to standard and investigational therapies. We highlight epigenetic profiling and integrated diagnosis as an essential component of classifying PA.

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Section: High Risk Features Of Pamentioning

confidence: 99%

Adult pilocytic astrocytoma in the molecular era: a comprehensive review

et al. 2021

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“…Among the 1155 prospective samples tested, Capper et al ( 35 ) reported 88% of classified cases (with calibrated scores of at least 0.9). In the same way, Jaunmuktane et al ( 32 ) reported a rate of 56% of CNS tumors matching a known MC (with calibrated scores of at least 0.84), while Lucas et al ( 44 ) reported 40% of match cases (with calibrated scores of at least 0.9) in a cohort of low-grade neuroepithelial tumors. Moreover, Karimi et al ( 43 ) reported that 84% of the cases tested with this tool had a clinically significant change in the histopathological diagnosis, with 15% of all those cases associated with a change in clinical decision-making for the patient.…”

Section: Discussionmentioning

confidence: 89%

Analyses of DNA Methylation Profiling in the Diagnosis of Intramedullary Astrocytomas

Lebrun

Bizet

Meléndez

et al. 2021

Journal of Neuropathology &Amp; Experimental Neurology

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Intramedullary astrocytomas (IMAs) consist of a heterogeneous group of rare central nervous system (CNS) tumors associated with variable outcomes. A DNA methylation-based classification approach has recently emerged as a powerful tool to further classify CNS tumors. However, no DNA methylation-related studies specifically addressing to IMAs have been performed yet. In the present study, we analyzed 16 IMA samples subjected to morphological and molecular analyses, including DNA methylation profiling. Among the 16 samples, only 3 cases were classified in a reference methylation class (MC) with the recommended calibrated score (≥0.9). The remaining cases were either considered “no-match” cases (calibrated score <0.3, n = 7) or were classified with low calibrated scores (ranging from 0.32 to 0.53, n = 6), including inconsistent classification. To obtain a more comprehensive tool for pathologists, we used different unsupervised analyses of DNA methylation profiles, including our data and those from the Heidelberg reference cohort. Even though our cohort included only 16 cases, hypotheses regarding IMA-specific classification were underlined; a potential specific MC of PA_SPINE was identified and high-grade IMAs, probably consisting of H3K27M wild-type IMAs, were mainly associated with ANA_PA MC. These hypotheses strongly suggest that a specific classification for IMAs has to be investigated.

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“…A subset of RGNT may lack this biphasic appearance and contain a predominantly oligodendroglioma-like or PA-like histology. 56 , 57 Indeed, 3 of 10 methylation-defined RGNT in a recent report were initially characterized as “low-grade oligodendroglial tumor NOS (not otherwise specified)” and lacked the characteristic neurocytic rosettes. 57 Genetically, RGNT are among the FGFR1 -altrered spectrum of LGG/LGNT and harbor either an FGFR1 p.N546 or p.K656 mutation, identified in 40 of 40 methylation-defined cases to date.…”

Section: Glioneuronal Tumorsmentioning

confidence: 99%

DNA methylation profiling as a model for discovery and precision diagnostics in neuro-oncology

2021

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Recent years have witnessed a shift to more objective and biologically-driven methods for central nervous system (CNS) tumor classification. The 2016 world health organization (WHO) classification update (“blue book”) introduced molecular diagnostic criteria into the definitions of specific entities as a response to the plethora of evidence that key molecular alterations define distinct tumor types and are clinically meaningful. While in the past such diagnostic alterations included specific mutations, copy number changes, or gene fusions, the emergence of DNA methylation arrays in recent years has similarly resulted in improved diagnostic precision, increased reliability, and has provided an effective framework for the discovery of new tumor types. In many instances, there is an intimate relationship between these mutations/fusions and DNA methylation signatures. The adoption of methylation data into neuro-oncology nosology has been greatly aided by the availability of technology compatible with clinical diagnostics, along with the development of a freely accessible machine learning-based classifier. In this review, we highlight the utility of DNA methylation profiling in CNS tumor classification with a focus on recently described novel and rare tumor types, as well as its contribution to refining existing types.

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Comprehensive analysis of diverse low-grade neuroepithelial tumors with FGFR1 alterations reveals a distinct molecular signature of rosette-forming glioneuronal tumor

Cited by 40 publications

References 44 publications

Adult pilocytic astrocytoma in the molecular era: a comprehensive review

Adult pilocytic astrocytoma in the molecular era: a comprehensive review

Analyses of DNA Methylation Profiling in the Diagnosis of Intramedullary Astrocytomas

DNA methylation profiling as a model for discovery and precision diagnostics in neuro-oncology

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