14 results on '"Tauziède-Espariat, Arnault"'
Search Results
2. Diagnostic Accuracy of a Reduced Immunohistochemical Panel in Medulloblastoma Molecular Subtyping, Correlated to DNA-methylation Analysis.
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Tauziède-Espariat A, Huybrechts S, Indersie E, Dufour C, Puget S, Chivet A, Roux A, Pagès M, Gareton A, Chrétien F, Lechapt E, Ayrault O, and Varlet P
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- Adaptor Proteins, Signal Transducing analysis, Cerebellar Neoplasms chemistry, Cerebellar Neoplasms genetics, Cerebellar Neoplasms pathology, Humans, In Situ Hybridization, Fluorescence, Medulloblastoma chemistry, Medulloblastoma genetics, Medulloblastoma pathology, Otx Transcription Factors analysis, Predictive Value of Tests, Reproducibility of Results, Retrospective Studies, Transcription Factors analysis, YAP-Signaling Proteins, beta Catenin analysis, Biomarkers, Tumor analysis, Biomarkers, Tumor genetics, Cerebellar Neoplasms classification, DNA Methylation, Immunohistochemistry, Medulloblastoma classification
- Abstract
Medulloblastomas (MBs) are the most frequent childhood malignant brain tumor. Four histopathologic variants and 4 genetic subgroups have been defined in the World Health Organization (WHO) 2016 Classification and constitute major risk stratification items directly affecting the patient management. Although MB subgroups have been molecularly defined, immunohistochemical surrogates are needed. The aim of our retrospective study was to evaluate the concordance between immunohistochemistry, using 4 antibodies (YAP1, GAB1, OTX2, and β-catenin), and DNA-methylation profiling in MB subgrouping. From a series of 155 MBs, the κ coefficient of concordance was almost perfect (0.90), with only 8/152 discrepant cases (no DNA-methylation analysis was available in 3 cases). Interestingly, the discrepancies mostly concerned (7/8 cases) MBs with divergent differentiations (myogenic, melanotic, and others) with all of those classified into group 3 (n=6) and group 4 (n=1) by DNA-methylation profiling. Another discrepant case concerned a WNT-activated MB (showing only 1% of immunopositive tumor cell nuclei), highlighting the difficulties of determining an appropriate β-catenin immunostaining cutoff. The high concordance of the routine immunohistochemical panel (YAP1, GAB1, OTX2, and β-catenin) and DNA-methylation profiling confirm its utility as a reliable predictive marker of molecular subtype in MBs. We analyzed the accuracy of 10 different IHC combinations for the determination of MB subtype and found that a combination of 2 antibodies (YAP1 and OTX2) allows for the successful characterization of 144 cases of 152 cases. Finally, our series extends the molecular data of the rare morphologic variant of MBs with melanotic/myogenic differentiations., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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3. Diagnostics of pediatric supratentorial RELA ependymomas: integration of information from histopathology, genetics, DNA methylation and imaging.
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Pagès M, Pajtler KW, Puget S, Castel D, Boddaert N, Tauziède-Espariat A, Picot S, Debily MA, Kool M, Capper D, Sainte-Rose C, Chrétien F, Pfister SM, Pietsch T, Grill J, Varlet P, and Andreiuolo F
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- Brain Neoplasms pathology, Child, Child, Preschool, Ependymoma metabolism, Ependymoma pathology, Female, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence methods, Infant, Male, NF-kappa B metabolism, Proteins genetics, Proteins metabolism, Supratentorial Neoplasms metabolism, Supratentorial Neoplasms pathology, Transcription Factor RelA metabolism, DNA Methylation, Ependymoma diagnosis, Ependymoma genetics, Supratentorial Neoplasms diagnosis, Supratentorial Neoplasms genetics, Transcription Factor RelA genetics
- Abstract
Ependymoma with RELA fusion has been defined as a novel entity of the revised World Health Organization 2016 classification of tumors of the central nervous system (CNS), characterized by fusion transcripts of the RELA gene and consequent pathological activation of the NFkB pathway. These tumors represent the majority of supratentorial ependymomas in children. The validation of diagnostic tools to identify this clinically relevant ependymoma entity is essential. Here, we have used interphase fluorescent in situ hybridization (FISH) for C11orf95 and RELA, immunohistochemistry (IHC) for p65-RelA and the recently developed DNA methylation-based classification besides conventional histopathology, and compared the precision of the methods in 40 supratentorial pediatric brain tumors diagnosed as ependymomas in the past years. Reverse transcription PCR (RT-PCR) and RNA sequencing were performed to explore discordant cases. Furthermore, we integrated imaging and clinical features as additional layers of information. The concordance between nuclear RelA expression by IHC and RELA FISH was 100%. Concordance between IHC and DNA methylation profiling, and between FISH and DNA methylation profiling was also high (96.4% and 95.2%, respectively). Thirty-four out of 40 (85%) cases were confirmed by integrated diagnoses as ependymal tumors, including 22 RELA-fused ependymomas (71% of ependymal tumors), two YAP1-fused ependymomas (6%), six non-RELA/non-YAP1 ependymomas (18%) and four ependymal/subependymal mixed tumors (12%). Ependymal/subependymal mixed tumors had an excellent clinical outcome despite the presence of histopathological signs of malignancy, suggesting that these tumors should not be diagnosed as classic ependymomas. DNA methylation profiling helped in the differential diagnosis of RELA-fused ependymomas. IHC and FISH, which are available in the majority of pathology laboratories, are valuable tools to identify RELA-fused ependymomas., (© 2018 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)
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- 2019
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4. Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions
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Bogumil, Henri, Sill, Martin, Schrimpf, Daniel, Ismer, Britta, Blume, Christina, Rahmanzade, Ramin, Hinz, Felix, Cherkezov, Asan, Banan, Rouzbeh, Friedel, Dennis, Reuss, David E., Selt, Florian, Ecker, Jonas, Milde, Till, Pajtler, Kristian W., Schittenhelm, Jens, Hench, Jürgen, Frank, Stephan, Boldt, Henning B., Kristensen, Bjarne Winther, Scheie, David, Melchior, Linea C., Olesen, Viola, Sehested, Astrid, Boué, Daniel R., Abdullaev, Zied, Satgunaseelan, Laveniya, Kurth, Ina, Seidlitz, Annekatrin, White, Christine L., Ng, Ho-Keung, Shi, Zhi-Feng, Haberler, Christine, Deckert, Martina, Timmer, Marco, Goldbrunner, Roland, Tauziède-Espariat, Arnault, Varlet, Pascale, Brandner, Sebastian, Alexandrescu, Sanda, Snuderl, Matija, Aldape, Kenneth, Korshunov, Andrey, Witt, Olaf, Herold-Mende, Christel, Unterberg, Andreas, Wick, Wolfgang, Pfister, Stefan M., von Deimling, Andreas, Jones, David T. W., Sahm, Felix, and Sievers, Philipp
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- 2023
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5. CNS tumors with PLAGL1-fusion: beyond ZFTA and YAP1 in the genetic spectrum of supratentorial ependymomas.
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Tauziède-Espariat, Arnault, Nicaise, Yvan, Sievers, Philipp, Sahm, Felix, von Deimling, Andreas, Guillemot, Delphine, Pierron, Gaëlle, Duchesne, Mathilde, Edjlali, Myriam, Dangouloff-Ros, Volodia, Boddaert, Nathalie, Roux, Alexandre, Dezamis, Edouard, Hasty, Lauren, Lhermitte, Benoît, Hirsch, Edouard, Hirsch, Maria Paola Valenti, Ardellier, François-Daniel, Karnoub, Mélodie-Anne, and Csanyi, Marie
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FLUORESCENCE in situ hybridization , *DNA methylation , *RNA sequencing , *BRAIN tumors , *ELECTRON microscopy - Abstract
A novel methylation class, "neuroepithelial tumor, with PLAGL1 fusion" (NET-PLAGL1), has recently been described, based on epigenetic features, as a supratentorial pediatric brain tumor with recurrent histopathological features suggesting an ependymal differentiation. Because of the recent identification of this neoplastic entity, few histopathological, radiological and clinical data are available. Herein, we present a detailed series of nine cases of PLAGL1-fused supratentorial tumors, reclassified from a series of supratentorial ependymomas, non-ZFTA/non-YAP1 fusion-positive and subependymomas of the young. This study included extensive clinical, radiological, histopathological, ultrastructural, immunohistochemical, genetic and epigenetic (DNA methylation profiling) data for characterization. An important aim of this work was to evaluate the sensitivity and specificity of a novel fluorescent in situ hybridization (FISH) targeting the PLAGL1 gene. Using histopathology, immunohistochemistry and electron microscopy, we confirmed the ependymal differentiation of this new neoplastic entity. Indeed, the cases histopathologically presented as "mixed subependymomas-ependymomas" with well-circumscribed tumors exhibiting a diffuse immunoreactivity for GFAP, without expression of Olig2 or SOX10. Ultrastructurally, they also harbored features reminiscent of ependymal differentiation, such as cilia. Different gene partners were fused with PLAGL1: FOXO1, EWSR1 and for the first time MAML2. The PLAGL1 FISH presented a 100% sensitivity and specificity according to RNA sequencing and DNA methylation profiling results. This cohort of supratentorial PLAGL1-fused tumors highlights: 1/ the ependymal cell origin of this new neoplastic entity; 2/ benefit of looking for a PLAGL1 fusion in supratentorial cases of non-ZFTA/non-YAP1 ependymomas; and 3/ the usefulness of PLAGL1 FISH. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Imaging features to distinguish posterior fossa ependymoma subgroups.
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Leclerc, Thomas, Levy, Raphael, Tauziède-Espariat, Arnault, Roux, Charles-Joris, Beccaria, Kevin, Blauwblomme, Thomas, Puget, Stéphanie, Grill, Jacques, Dufour, Christelle, Guerrini-Rousseau, Léa, Abbou, Samuel, Bolle, Stéphanie, Roux, Alexandre, Pallud, Johan, Provost, Corentin, Oppenheim, Catherine, Varlet, Pascale, Boddaert, Nathalie, and Dangouloff-Ros, Volodia
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EPENDYMOMA ,CENTRAL nervous system cancer ,POSTERIOR cranial fossa ,FISHER exact test ,DNA methylation - Abstract
Objectives: Posterior fossa ependymoma group A (EPN_PFA) and group B (EPN_PFB) can be distinguished by their DNA methylation and give rise to different prognoses. We compared the MRI characteristics of EPN_PFA and EPN_PFB at presentation. Methods: Preoperative imaging of 68 patients with posterior fossa ependymoma from two centers was reviewed by three independent readers, blinded for histomolecular grouping. Location, tumor extension, tumor volume, hydrocephalus, calcifications, tissue component, enhancement or diffusion signal, and histopathological data (cellular density, calcifications, necrosis, mitoses, vascularization, and microvascular proliferation) were compared between the groups. Categorical data were compared between groups using Fisher's exact tests, and quantitative data using Mann–Whitney tests. We performed a Benjamini–Hochberg correction of the p values to account for multiple tests. Results: Fifty-six patients were categorized as EPN_PFA and 12 as EPN_PFB, with median ages of 2 and 20 years, respectively (p = 0.0008). The median EPN_PFA tumoral volume was larger (57 vs 29 cm
3 , p = 0.003), with more pronounced hydrocephalus (p = 0.002). EPN_PFA showed an exclusive central position within the 4th ventricle in 61% of patients vs 92% for EPN_PFB (p = 0.01). Intratumor calcifications were found in 93% of EPN_PFA vs 40% of EPN_PFB (p = 0.001). Invasion of the posterior fossa foramina was mostly found for EPN_PFA, particularly the foramina of Luschka (p = 0.0008). EPN_PFA showed whole and homogeneous tumor enhancement in 5% vs 75% of EPN_PFB (p = 0.0008). All mainly cystic tumors were EPN_PFB (p = 0.002). The minimal and maximal relative ADC was slightly lower in EPN_PFA (p = 0.02 and p = 0.01, respectively). Conclusion: Morphological characteristics from imaging differ between posterior fossa ependymoma subtypes and may help to distinguish them preoperatively. Clinical relevance statement: This study provides a tool to differentiate between group A and group B ependymomas, which will ultimately allow the therapeutic strategy to be adapted in the early stages of patient management. Key Points: • Posterior fossa ependymoma subtypes often have different imaging characteristics. • Posterior fossa ependymomas group A are commonly median or lateral tissular calcified masses, with incomplete enhancement, affecting young children and responsible for pronounced hydrocephalus and invasion of the posterior fossa foramina. • Posterior fossa ependymomas group B are commonly median non-calcified masses of adolescents and adults, predominantly cystic, and minimally invasive, with total and homogeneous enhancement. [ABSTRACT FROM AUTHOR]- Published
- 2024
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7. Pediatric-type high-grade neuroepithelial tumors with CIC gene fusion share a common DNA methylation signature.
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Sievers, Philipp, Sill, Martin, Schrimpf, Daniel, Abdullaev, Zied, Donson, Andrew M., Lake, Jessica A., Friedel, Dennis, Scheie, David, Tynninen, Olli, Rauramaa, Tuomas, Vepsäläinen, Kaisa L., Samuel, David, Chapman, Rebecca, Grundy, Richard G., Pajtler, Kristian W., Tauziède-Espariat, Arnault, Métais, Alice, Varlet, Pascale, Snuderl, Matija, and Jacques, Thomas S.
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GENE fusion ,DNA methylation ,CENTRAL nervous system tumors ,NEUROECTODERMAL tumors ,CENTRAL nervous system injuries ,RNA sequencing - Abstract
Pediatric neoplasms in the central nervous system (CNS) show extensive clinical and molecular heterogeneity and are fundamentally different from those occurring in adults. Molecular genetic testing contributes to accurate diagnosis and enables an optimal clinical management of affected children. Here, we investigated a rare, molecularly distinct type of pediatric high-grade neuroepithelial tumor (n = 18), that was identified through unsupervised visualization of genome-wide DNA methylation array data, together with copy number profiling, targeted next-generation DNA sequencing, and RNA transcriptome sequencing. DNA and/or RNA sequencing revealed recurrent fusions involving the capicua transcriptional repressor (CIC) gene in 10/10 tumor samples analyzed, with the most common fusion being CIC::LEUTX (n = 9). In addition, a CIC::NUTM1 fusion was detected in one of the tumors. Apart from the detected fusion events, no additional oncogenic alteration was identified in these tumors. The histopathological review demonstrated a morphologically heterogeneous group of high-grade neuroepithelial tumors with positive immunostaining for markers of glial differentiation in combination with weak and focal expression of synaptophysin, CD56 and CD99. All tumors were located in the supratentorial compartment, occurred during childhood (median age 8.5 years) and typically showed early relapses. In summary, we expand the spectrum of pediatric-type tumors of the CNS by reporting a previously uncharacterized group of rare high-grade neuroepithelial tumors that share a common DNA methylation signature and recurrent gene fusions involving the transcriptional repressor CIC. Downstream functional consequences of the fusion protein CIC::LEUTX and potential therapeutic implications need to be further investigated. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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8. NTRK‐rearranged spindle cell neoplasms are ubiquitous tumours of myofibroblastic lineage with a distinct methylation class.
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Tauziède‐Espariat, Arnault, Duchesne, Mathilde, Baud, Jessica, Le Quang, Mégane, Bochaton, Dorian, Azmani, Rihab, Croce, Sabrina, Hostein, Isabelle, Kesrouani, Carole, Guillemot, Delphine, Pierron, Gaëlle, Bourdeaut, Franck, Cardoen, Liesbeth, Hasty, Lauren, Lechapt, Emmanuèle, Métais, Alice, Chrétien, Fabrice, Puget, Stéphanie, Varlet, Pascale, and Le Loarer, François
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ANAPLASTIC lymphoma kinase , *GENE fusion , *CENTRAL nervous system , *DNA methylation , *HIERARCHICAL clustering (Cluster analysis) , *TUMORS , *METHYLATION - Abstract
Aims: NTRK gene fusions have been described in a wide variety of central nervous system (CNS) and soft tissue tumours, including the provisional tumour type 'spindle cell neoplasm, NTRK‐rearranged' (SCN–NTRK), added to the 2020 World Health Organisation Classification of Soft Tissue Tumours. Because of histopathological and molecular overlaps with other soft tissue entities, controversy remains concerning the lineage and terminology of SCN–NTRK. Methods and results: This study included 16 mesenchymal tumours displaying kinase gene fusions (NTRK fusions and one MET fusion) initially diagnosed as infantile fibrosarcomas (IFS), SCN–NTRK and adult‐type fibrosarcomas from the soft tissue, viscera and CNS. We used immunohistochemistry, DNA methylation profiling, whole RNA‐sequencing and ultrastructural analysis to characterise them. Unsupervised t‐distributed stochastic neighbour embedding analysis showed that 11 cases (two CNS tumours and nine extra‐CNS) formed a unique and new methylation cluster, while all tumours but one, initially diagnosed as IFS, clustered in a distinct methylation class. All the tumours except one formed a single cluster within the hierarchical clustering of whole RNA‐sequencing data. Tumours from the novel methylation class co‐expressed CD34 and S100, had variable histopathological grades and frequently displayed a CDKN2A deletion. Ultrastructural analyses evidenced a myofibroblastic differentiation. Conclusions: Our findings confirm that SCN‐NTRK share similar features in adults and children and in all locations combine an infiltrative pattern, distinct epigenetic and transcriptomic profiles, and ultrastructural evidence of a myofibroblastic lineage. Further studies may support the use of new terminology to better describe their myofibroblastic nature. [ABSTRACT FROM AUTHOR]
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- 2023
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9. The genomic landscape of dysembryoplastic neuroepithelial tumours and a comprehensive analysis of recurrent cases.
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Pagès, Mélanie, Debily, Marie‐Anne, Fina, Frédéric, Jones, David T. W., Saffroy, Raphael, Castel, David, Blauwblomme, Thomas, Métais, Alice, Bourgeois, Marie, Lechapt‐Zalcman, Emmanuèle, Tauziède‐Espariat, Arnault, Andreiuolo, Felipe, Chrétien, Fabrice, Grill, Jacques, Boddaert, Nathalie, Figarella‐Branger, Dominique, Beroukhim, Rameen, and Varlet, Pascale
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DNA methylation ,TUMORS ,CELLULAR signal transduction ,EPIGENOMICS ,ASTROCYTOMAS ,GLIOMAS - Abstract
Aims: Dysembryoplastic neuroepithelial tumour (DNT) is a glioneuronal tumour that is challenging to diagnose, with a wide spectrum of histological features. Three histopathological patterns have been described: specific DNTs (both the simple form and the complex form) comprising the specific glioneuronal element, and also the non‐specific/diffuse form which lacks it, and has unclear phenotype–genotype correlations with numerous differential diagnoses. Methods: We used targeted methods (immunohistochemistry, fluorescence in situ hybridisation and targeted sequencing) and large‐scale genomic methodologies including DNA methylation profiling to perform an integrative analysis to better characterise a large retrospective cohort of 82 DNTs, enriched for tumours that showed progression on imaging. Results: We confirmed that specific DNTs are characterised by a single driver event with a high frequency of FGFR1 variants. However, a subset of DNA methylation‐confirmed DNTs harbour alternative genomic alterations to FGFR1 duplication/mutation. We also demonstrated that a subset of DNTs sharing the same FGFR1 alterations can show in situ progression. In contrast to the specific forms, "non‐specific/diffuse DNTs" corresponded to a heterogeneous molecular group encompassing diverse, newly‐described, molecularly distinct entities. Conclusions: Specific DNT is a homogeneous group of tumours sharing characteristics of paediatric low‐grade gliomas: a quiet genome with a recurrent genomic alteration in the RAS‐MAPK signalling pathway, a distinct DNA methylation profile and a good prognosis but showing progression in some cases. The "non‐specific/diffuse DNTs" subgroup encompasses various recently described histomolecular entities, such as PLNTY and diffuse astrocytoma, MYB or MYBL1 altered. [ABSTRACT FROM AUTHOR]
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- 2022
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10. Rosette‐forming glioneuronal tumours are midline, FGFR1‐mutated tumours.
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Appay, Romain, Bielle, Franck, Sievers, Philipp, Barets, Doriane, Fina, Frédéric, Boutonnat, Jean, Adam, Clovis, Gauchotte, Guillaume, Godfraind, Catherine, Lhermitte, Benoît, Maurage, Claude‐Alain, Meyronet, David, Mokhtari, Karima, Rousseau, Audrey, Tauziède‐Espariat, Arnault, Tortel, Marie‐Claire, Uro‐Coste, Emmanuelle, Burel‐Vandenbos, Fanny, Chotard, Guillaume, and Pesce, Florian
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BRAIN tumors ,DNA methylation ,TUMORS - Abstract
Aim: Rosette‐forming glioneuronal tumour (RGNT) is a rare central nervous system (CNS) World Health Organization (WHO) grade 1 brain neoplasm. According to the WHO 2021, essential diagnostic criteria are a 'biphasic histomorphology with neurocytic and a glial component, and uniform neurocytes forming rosettes and/or perivascular pseudorosettes associated with synaptophysin expression' and/or DNA methylation profile of RGNT whereas 'FGFR1 mutation with co‐occurring PIK3CA and/or NF1 mutation' are desirable criteria. Material and methods: We report a series of 46 cases fulfilling the essential pathological diagnostic criteria for RGNT. FGFR1 and PIK3CA hotspot mutations were searched for by multiplexed digital PCR in all cases, whereas DNA methylation profiling and/or PIK3R1 and NF1 alterations were analysed in a subset of cases. Results: Three groups were observed. The first one included 21 intracranial midline tumours demonstrating FGFR1 mutation associated with PIK3CA or PIK3R1 (n = 19) or NF1 (n = 1) or PIK3CA and NF1 (n = 1) mutation. By DNA methylation profiling, eight cases were classified as RGNT (they demonstrated FGFR1 and PIK3CA or PIK3R1 mutations). Group 2 comprised 11 cases associated with one single FGFR1 mutation. Group 3 included six cases classified as low‐grade glioma (LGG) other than RGNT (one‐sixth showed FGFR1 mutation and one a FGFR1 and NF1 mutation) and eight cases without FGFR1 mutation. Groups 2 and 3 were enriched in lateral and spinal cases. Conclusions: We suggest adding FGFR1 mutation and intracranial midline location as essential diagnostic criteria. When DNA methylation profiling is not available, a RGNT diagnosis remains certain in cases demonstrating characteristic pathological features and FGFR1 mutation associated with either PIK3CA or PIK3R1 mutation. [ABSTRACT FROM AUTHOR]
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- 2022
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11. The dural angioleiomyoma harbors frequent GJA4 mutation and a distinct DNA methylation profile.
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Tauziède-Espariat, Arnault, Pierre, Thibaut, Wassef, Michel, Castel, David, Riant, Florence, Grill, Jacques, Roux, Alexandre, Pallud, Johan, Dezamis, Edouard, Bresson, Damien, Benichi, Sandro, Blauwblomme, Thomas, Benzohra, Djallel, Gauchotte, Guillaume, Pouget, Celso, Colnat-Coulbois, Sophie, Mokhtari, Karima, Balleyguier, Corinne, Larousserie, Frédérique, and Dangouloff-Ros, Volodia
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DNA methylation , *HIERARCHICAL clustering (Cluster analysis) , *ANAPLASTIC lymphoma kinase , *METHYLATION , *CENTRAL nervous system , *HARBORS , *ARTERIOVENOUS malformation - Abstract
The International Society for the Study of Vascular Anomalies (ISSVA) has defined four vascular lesions in the central nervous system (CNS): arteriovenous malformations, cavernous angiomas (also known as cerebral cavernous malformations), venous malformations, and telangiectasias. From a retrospective central radiological and histopathological review of 202 CNS vascular lesions, we identified three cases of unclassified vascular lesions. Interestingly, they shared the same radiological and histopathological features evoking the cavernous subtype of angioleiomyomas described in the soft tissue. We grouped them together with four additional similar cases from our clinicopathological network and performed combined molecular analyses. In addition, cases were compared with a cohort of 5 soft tissue angioleiomyomas. Three out 6 CNS lesions presented the same p.Gly41Cys GJA4 mutation recently reported in hepatic hemangiomas and cutaneous venous malformations and found in 4/5 soft tissue angioleiomyomas of our cohort with available data. Most DNA methylation profiles were not classifiable using the CNS brain tumor (version 12.5), and sarcoma (version 12.2) classifiers. However, using unsupervised t-SNE analysis and hierarchical clustering analysis, 5 of the 6 lesions grouped together and formed a distinct epigenetic group, separated from the clusters of soft tissue angioleiomyomas, other vascular tumors, inflammatory myofibroblastic tumors and meningiomas. Our extensive literature review identified several cases similar to these lesions, with a wide variety of denominations. Based on radiological and histomolecular findings, we suggest the new terminology of "dural angioleiomyomas" (DALM) to designate these lesions characterized by a distinct DNA methylation pattern and frequent GJA4 mutations. [ABSTRACT FROM AUTHOR]
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- 2022
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12. Intra‐ and extra‐cranial BCOR‐ITD tumours are separate entities within the BCOR‐rearranged family.
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Bouchoucha, Yassine, Tauziède‐Espariat, Arnault, Gauthier, Arnaud, Guillemot, Delphine, Bochaton, Dorian, Vibert, Julien, Carton, Matthieu, Watson, Sarah, Grossetête, Sandrine, Quignot, Chloé, Orbach, Daniel, Corradini, Nadège, Schleiermacher, Gudrun, Bourdeaut, Franck, Simbozel, Marie, Dufour, Christelle, Minard‐Colin, Véronique, Brahmi, Mehdi, Tirode, Franck, and Pissaloux, Daniel
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PROGRESSION-free survival ,ENDOMETRIUM ,TUMORS ,CENTRAL nervous system ,DNA methylation ,OVERALL survival ,DNA sequencing - Abstract
BCOR‐ITD tumours form an emerging family of aggressive entities with an internal tandem duplication (ITD) in the last exon of the BCOR gene. The family includes cerebral tumours, termed central nervous system BCOR‐ITD (CNS BCOR‐ITD), and sarcomatous types described in the kidney as clear cell sarcoma of the kidney (CCSK), in the endometrium as high‐grade endometrial stromal sarcoma, and in the bone and soft tissue as undifferentiated round cell sarcoma or primitive myxoid mesenchymal tumour of infancy. Based on a series of 33 retrospective cases, including 10 CNS BCOR‐ITD and 23 BCOR‐ITD sarcomas, we interrogated the homogeneity of the entity regarding clinical, radiological, and histopathological findings, and molecular signatures. Whole‐transcriptomic sequencing and DNA methylation profiling were used for unsupervised clustering. BCOR‐ITD tumours mostly affected young children with a median age at diagnosis of 2.1 years (range 0–62.4). Median overall survival was 3.9 years and progression‐free survival was 1.4 years. This dismal prognosis is shared among tumours in all locations except CCSK. Histopathological review revealed marked differences between CNS BCOR‐ITD and BCOR‐ITD sarcomas. These two groups were consistently segregated by unsupervised clustering of expression (n = 22) and DNA methylation (n = 21) data. Proximity between the two groups may result from common somatic changes within key pathways directly related to the novel activity of the ITD itself. Conversely, comparison of gene signatures with single‐cell RNA‐Seq atlases suggests that the distinction between BCOR‐ITD sarcomas and CNS BCOR‐ITD may result from differences in cells of origin. [ABSTRACT FROM AUTHOR]
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- 2022
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13. A novel LARGE1-AFF2 fusion expanding the molecular alterations associated with the methylation class of neuroepithelial tumors with PATZ1 fusions.
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Tauziède-Espariat, Arnault, Chotard, Guillaume, le Loarer, François, Baud, Jessica, Azmani, Rihab, Dangouloff-Ros, Volodia, Boddaert, Nathalie, Icher-de-Bouyn, Céline, Gimbert, Edouard, Hasty, Lauren, Métais, Alice, Chrétien, Fabrice, and Varlet, Pascale
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SARCOMA , *METHYLATION , *DNA methylation , *TUMOR suppressor genes ,CENTRAL nervous system tumors - Abstract
A novel DNA methylation class of tumor within the central nervous system, the "neuroepithelial tumor (NET), PATZ1 fusion-positive" has recently been identified in the literature, characterized by EWSR1- and MN1-PATZ1 fusions. The cellular origin of this tumor type remains unknown, wavering between glioneuronal or mesenchymal (as round cell sarcomas with EWSR1-PATZ1 of the soft tissue). Because of the low number of reported cases, this tumor type will not be added to the 2021 World Health Organization Classification of Tumors of the Central Nervous System (CNS). Herein, we report one case of a CNS tumor classified by DNA methylation analysis as NET-PATZ1 but harboring a novel LARGE1-AFF2 fusion which has until now never been described in soft tissue or the CNS. We compare its clinical, histopathological, immunophenotypical, and genetic features with those previously described in NET-PATZ1. Interestingly, the current case presented histopathological (astroblastoma-like features, glioneuronal phenotype), clinical (with a favorable course), genetic (1p loss), and epigenetic (DNA-methylation profiling) similarities to previously reported cases of NET-PATZ1. Our results added data suggesting that different histomolecular tumor subtypes seem to be included within the methylation class "NET, PATZ1 fusion-positive", including non PATZ1 fusions, and that further cases are needed to better characterize them. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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14. The histomolecular criteria established for adult anaplastic pilocytic astrocytoma are not applicable to the pediatric population.
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Gareton, Albane, Tauziède-Espariat, Arnault, Dangouloff-Ros, Volodia, Roux, Alexandre, Saffroy, Raphaël, Castel, David, Kergrohen, Thomas, Fina, Fréderic, Figarella-Branger, Dominique, Pagès, Mélanie, Bourdeaut, Franck, Doz, François, Puget, Stéphanie, Dufour, Christelle, Lechapt, Emmanuèle, Chrétien, Fabrice, Grill, Jacques, and Varlet, Pascale
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ASTROCYTOMAS , *DNA methylation , *GLIOBLASTOMA multiforme , *DNA fingerprinting , *EXCEPTIONAL children , *BIOLOGICAL tags - Abstract
Pilocytic astrocytoma (PA) is the most common pediatric glioma, arising from a single driver MAPK pathway alteration. Classified as a grade I tumor according to the 2016 WHO classification, prognosis is excellent with a 10-year survival rate > 95% after surgery. However, rare cases present with anaplastic features, including an unexpected high mitotic/proliferative index, thus posing a diagnostic and therapeutic challenge. Based on small histomolecular series and case reports, such tumors arising at the time of diagnosis or recurrence have been designated by many names including pilocytic astrocytoma with anaplastic features (PAAF). Recent DNA methylation-profiling studies performed mainly on adult cases have revealed that PAAF exhibit a specific methylation signature, thus constituting a distinct methylation class from typical PA [methylation class anaplastic astrocytoma with piloid features—(MC-AAP)]. However, the diagnostic and prognostic significance of MC-AAP remains to be determined in children. We performed an integrative work on the largest pediatric cohort of PAAF, defined according to strict criteria: morphology compatible with the diagnosis of PA, with or without necrosis, ≥ 4 mitoses for 2.3 mm2, and MAPK pathway alteration. We subjected 31 tumors to clinical, imaging, morphological and molecular analyses, including DNA methylation profiling. We identified only one tumor belonging to the MC-AAP (3%), the others exhibiting a methylation profile typical for PA (77%), IDH-wild-type glioblastoma (7%), and diffuse leptomeningeal glioneuronal tumor (3%), while three cases (10%) did not match to a known DNA methylation class. No significant outcome differences were observed between PAAF with necrosis versus no necrosis (p = 0.07), or with 4–6 mitoses versus 7 or more mitoses (p = 0.857). Our findings argue that the diagnostic histomolecular criteria established for anaplasia in adult PA are not of diagnostic or prognostic value in a pediatric setting. Further extensive and comprehensive integrative studies are necessary to accurately define this exceptional entity in children. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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