Clinical, radiological and molecular characterization of intramedullary astrocytomas

Lebrun, Laetitia; Meléndez, Bárbara; Blanchard, Oriane; Nève, Nancy De; Campenhout, Claude Van; Lelotte, Julie; Balériaux, Danielle; Riva, Mattéo; Brotchi, Jacques; Bruneau, Michaël; Witte, Olivier De; Decaestecker, Christine; D’Haene, Nicky; Salmon, Isabelle

doi:10.1186/s40478-020-00962-1

Cited by 25 publications

(60 citation statements)

References 55 publications

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“…The cohort consisted of 9 grade 1 pilocytic, 2 diffuse grade 2, 3 anaplastic grade 3 and 6 grade 4 IMAs. One case was diagnosed as low-grade IMA, as previously described ( 15 ). Two patients were included with initial (case 6 and case 8) and recurrent (rec) samples (case 6 rec and 8 rec).…”

Section: Methodsmentioning

confidence: 99%

“…In addition, we used 2 grade 2 intramedullary ependymomas as positive validation controls that were expected to be assigned in methylation class (MC) spine ependymoma (EPN_SPINE ( 28 )). Clinical variables such as event-free survival and overall survival were collected as previously described ( 15 ).…”

Section: Methodsmentioning

confidence: 99%

“…and I.S.) according to the WHO 2016 classification ( 6 ), as previously described ( 15 ). A detailed morphological analysis was performed for each case, including the presence of Rosenthal fibers, eosinophilic granular bodies, necrosis, the estimation of cellularity (low, moderate, high), atypia (low, moderate, high), vascularization, and descriptions of the tumor architecture (labeled as biphasic, piloid, oligodendroglioma-like, fascicular, or fibrillar).…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, the most frequent molecular alterations found in brain astrocytomas, such as IDH mutations, are generally not observed in IMAs or were not classic IDH1 p. R132H and IDH2 p. R172H mutations ( 9 , 11–17 ). In a previous study, we reported that classic molecular alterations observed in brain astrocytomas ( IDH mutations, EGFR alterations, and TERT promoter mutations) are very rare in IMAs, with rather poor prognosis associated with IDH mutations in low-grade IMAs ( 15 ). For high-grade IMAs, the majority of the tumors described in the literature were strongly related to H3K27M mutations ( 9 , 12 , 15 , 18–22 ).…”

Section: Introductionmentioning

confidence: 94%

“…In a previous study, we reported that classic molecular alterations observed in brain astrocytomas ( IDH mutations, EGFR alterations, and TERT promoter mutations) are very rare in IMAs, with rather poor prognosis associated with IDH mutations in low-grade IMAs ( 15 ). For high-grade IMAs, the majority of the tumors described in the literature were strongly related to H3K27M mutations ( 9 , 12 , 15 , 18–22 ).…”

Section: Introductionmentioning

confidence: 94%

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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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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 94%

See 3 more Smart Citations

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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Mutational landscape of primary spinal cord astrocytoma

Cheng

Zhang

Zhao

et al. 2023

The Journal of Pathology

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Primary spinal cord astrocytoma (SCA) is a rare disease. Knowledge about the molecular profiles of SCAs mostly comes from intracranial glioma; the pattern of genetic alterations of SCAs is not well understood. Herein, we describe genome‐sequencing analyses of primary SCAs, aiming to characterize the mutational landscape of primary SCAs. We utilized whole exome sequencing (WES) to analyze somatic nucleotide variants (SNVs) and copy number variants (CNVs) among 51 primary SCAs. Driver genes were searched using four algorithms. GISTIC2 was used to detect significant CNVs. Additionally, recurrently mutated pathways were also summarized. A total of 12 driver genes were identified. Of those, H3F3A (47.1%), TP53 (29.4%), NF1 (19.6%), ATRX (17.6%), and PPM1D (17.6%) were the most frequently mutated genes. Furthermore, three novel driver genes seldom reported in glioma were identified: HNRNPC, SYNE1, and RBM10. Several germline mutations, including three variants (SLC16A8 rs2235573, LMF1 rs3751667, FAM20C rs774848096) that were associated with risk of brain glioma, were frequently observed in SCAs. Moreover, 12q14.1 (13.7%) encompassing the oncogene CDK4 was recurrently amplified and negatively affected patient prognosis. Besides frequently mutated RTK/RAS pathway and PI3K pathway, the cell cycle pathway controlling the phosphorylation of retinoblastoma protein (RB) was mutated in 39.2% of patients. Overall, a considerable degree of the somatic mutation landscape is shared between SCAs and brainstem glioma. Our work provides a key insight into the molecular profiling of primary SCAs, which might represent candidate drug targets and complement the molecular atlas of glioma. © 2023 The Pathological Society of Great Britain and Ireland.

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Pediatric spinal pilocytic astrocytomas form a distinct epigenetic subclass from pilocytic astrocytomas of other locations and diffuse leptomeningeal glioneuronal tumours

et al. 2022

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Pediatric spinal low-grade glioma (LGG) and glioneuronal tumours are rare, accounting for less 2.8–5.2% of pediatric LGG. New tumour types frequently found in spinal location such as diffuse leptomeningeal glioneuronal tumours (DLGNT) have been added to the World Health Organization (WHO) classification of tumours of the central nervous system since 2016, but their distinction from others gliomas and particularly from pilocytic astrocytoma (PA) are poorly defined. Most large studies on this subject were published before the era of the molecular diagnosis and did not address the differential diagnosis between PAs and DLGNTs in this peculiar location. Our study retrospectively examined a cohort of 28 children with LGGs and glioneuronal intramedullary tumours using detailed radiological, clinico-pathological and molecular analysis. 25% of spinal PAs were reclassified as DLGNTs. PA and DLGNT are nearly indistinguishable in histopathology or neuroradiology. 83% of spinal DLGNTs presented first without leptomeningeal contrast enhancement. Unsupervised t-distributed stochastic neighbor embedding (t-SNE) analysis of DNA methylation profiles showed that spinal PAs formed a unique methylation cluster distinct from reference midline and posterior fossa PAs, whereas spinal DLGNTs clustered with reference DLGNT cohort. FGFR1 alterations were found in 36% of spinal tumours and were restricted to PAs. Spinal PAs affected significantly younger patients (median age 2 years old) than DLGNTs (median age 8.2 years old). Progression-free survival was similar among the two groups. In this location, histopathology and radiology are of limited interest, but molecular data (methyloma, 1p and FGFR1 status) represent important tools differentiating these two mitogen-activated protein kinase (MAPK) altered tumour types, PA and DLGNT. Thus, these molecular alterations should systematically be explored in this type of tumour in a spinal location.

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Clinical, radiological and molecular characterization of intramedullary astrocytomas

Cited by 25 publications

References 55 publications

Analyses of DNA Methylation Profiling in the Diagnosis of Intramedullary Astrocytomas

Analyses of DNA Methylation Profiling in the Diagnosis of Intramedullary Astrocytomas

Mutational landscape of primary spinal cord astrocytoma

Pediatric spinal pilocytic astrocytomas form a distinct epigenetic subclass from pilocytic astrocytomas of other locations and diffuse leptomeningeal glioneuronal tumours

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