Infratentorial C11orf95-fused gliomas share histologic, immunophenotypic, and molecular characteristics of supratentorial RELA-fused ependymoma

Keenan, Camille; Graham, Richard; Harreld, Julie H.; Lucas, John T.; Finkelstein, David; Wheeler, David A.; Li, Xiaoyü; Dalton, James; Upadhyaya, Santhosh A.; Raimondi, Susana C.; Boop, Frederick A.; DeCuypere, Michael; Zhang, Jinghui; Vinitsky, Anna; Wang, Lu; Chiang, Jason

doi:10.1007/s00401-020-02238-3

Cited by 16 publications

(18 citation statements)

References 8 publications

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“…In the CNS, the case of ST anaplastic ependymoma presenting clear cell morphology with C11orf95 ‐ NCOA1 was reported (5). Quite recently, Keenan et al reported three cases of “infratentorial” ependymomas with C11orf95 ‐ NCOA2 , ‐ MAML2 , or ‐ RELA showing histological features closely resembling ST ependymomas with C11orf95 ‐ RELA (35). DNA methylation analysis demonstrated that all these infratentorial ependymomas clustered together with ST ependymomas with C11orf95 ‐ RELA (35).…”

Section: Discussionmentioning

confidence: 99%

“…Quite recently, Keenan et al reported three cases of “infratentorial” ependymomas with C11orf95 ‐ NCOA2 , ‐ MAML2 , or ‐ RELA showing histological features closely resembling ST ependymomas with C11orf95 ‐ RELA (35). DNA methylation analysis demonstrated that all these infratentorial ependymomas clustered together with ST ependymomas with C11orf95 ‐ RELA (35). On the contrary, our study revealed that two ELTMDs with C11orf95 ‐ NCOA1/2 were epigenetically clearly distinct from ST ependymomas with C11orf95 ‐ RELA (Figure 5K).…”

Section: Discussionmentioning

confidence: 99%

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Ependymoma‐like tumor with mesenchymal differentiation harboring C11orf95‐NCOA1/2 or ‐RELA fusion: A hitherto unclassified tumor related to ependymoma

Tomomasa

Arai²,

Kawabata‐Iwakawa

et al. 2021

Brain Pathology

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Recurrent fusion genes involving C11orf95, C11orf95-RELA, have been identified only in supratentorial ependymomas among primary CNS tumors. Here, we report hitherto histopathologically unclassifiable high-grade tumors, under the tentative label of "ependymoma-like tumors with mesenchymal differentiation (ELTMDs)," harboring C11orf95-NCOA1/2 or -RELA fusion. We examined the clinicopathological and molecular features in five cases of ELTMDs.Except for one adult case (50 years old), all cases were in children ranging from 1 to 2.5 years old. All patients presented with a mass lesion in the cerebral hemisphere. Histologically, all cases demonstrated a similar histology with a mixture of components. The major components were embryonal-appearing components forming well-delineated tumor cell nests composed of small uniform cells with high proliferative activity, and spindle-cell mesenchymal components with a low-to high-grade sarcoma-like appearance. The embryonal-appearing components exhibited minimal ependymal differentiation including a characteristic EMA positivity and tubular structures, but histologically did not fit with ependymoma because they lacked perivascular pseudorosettes, a histological hallmark of ependymoma, formed well-delineated nests, and had diffuse and strong staining for CAM5.2. Molecular analysis identified C11orf95-NCOA1, -NCOA2, and -RELA in two, one, and two cases, respectively. t-distributed 2 of 14 | TOMOMASA eT Al.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ependymoma‐like tumor with mesenchymal differentiation harboring C11orf95‐NCOA1/2 or ‐RELA fusion: A hitherto unclassified tumor related to ependymoma

Tomomasa

Arai²,

Kawabata‐Iwakawa

et al. 2021

Brain Pathology

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“…Unique cases of ZFTA – MAML2 , ZFTA – RELA , and ZFTA – NCOA2 fusion in PF-EPN were reported recently. These tumors revealed characteristic ZFTA -mediated gene expression and whole-genome DNA methylation signatures corresponding to the ST-EPN-ZFTA group; accordingly, they were classified as “ST-EPN-ZFTA” despite the infratentorial localization [ 65 ].…”

Section: Molecular Profiles Of Pf-epnsmentioning

confidence: 99%

“…Given the existence of rare EPN subtypes e.g., PF-EPN with ZFTA rearrangement [ 65 ] or ST-EPN harboring ZFTA fusions with atypical (non- RELA ) partners, correct identification of a tumor with a particular group requires an extended diagnostic algorithm accounting for gene expression signatures. The creation of a universal diagnostic tool for the determination of molecular subtypes of EPN can be based on the analysis of gene expression signatures using the NanoString nCounter ® platform.…”

Section: Laboratory Approaches For Epn Diagnosticsmentioning

confidence: 99%

Molecular Stratification of Childhood Ependymomas as a Basis for Personalized Diagnostics and Treatment

Zaytseva

Papusha

Novichkova

et al. 2021

Cancers

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Ependymomas are among the most enigmatic tumors of the central nervous system, posing enormous challenges for pathologists and clinicians. Despite the efforts made, the treatment options are still limited to surgical resection and radiation therapy, while none of conventional chemotherapies is beneficial. While being histologically similar, ependymomas show considerable clinical and molecular diversity. Their histopathological evaluation alone is not sufficient for reliable diagnostics, prognosis, and choice of treatment strategy. The importance of integrated diagnosis for ependymomas is underscored in the recommendations of Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy. These updated recommendations were adopted and implemented by WHO experts. This minireview highlights recent advances in comprehensive molecular-genetic characterization of ependymomas. Strong emphasis is made on the use of molecular approaches for verification and specification of histological diagnoses, as well as identification of prognostic markers for ependymomas in children.

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“…Recently, recurrent fusions involving the pleomorphic adenoma gene-like 1 ( PLAGL1 ) gene have been discovered in a group of histopathologically diagnosed ST EPNs exhibiting a distinct DNA methylation profile [ 46 ], that occur mostly in children. To add complexity, rearrangements of ZFTA associated with RELA DNA methylation profiling have also been identified in EPN with an infratentorial location [ 47 , 48 ].…”

Section: Inter-tumoral Heterogeneity and Clinicopathological Characteristics Of Pediatric Intracranial Epn: A Brief Overviewmentioning

confidence: 99%

Cell-of-Origin and Genetic, Epigenetic, and Microenvironmental Factors Contribute to the Intra-Tumoral Heterogeneity of Pediatric Intracranial Ependymoma

Servidei

Lucchetti

Navarra

et al. 2021

Cancers

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Intra-tumoral heterogeneity (ITH) is a complex multifaceted phenomenon that posits major challenges for the clinical management of cancer patients. Genetic, epigenetic, and microenvironmental factors are concurrent drivers of diversity among the distinct populations of cancer cells. ITH may also be installed by cancer stem cells (CSCs), that foster unidirectional hierarchy of cellular phenotypes or, alternatively, shift dynamically between distinct cellular states. Ependymoma (EPN), a molecularly heterogeneous group of tumors, shows a specific spatiotemporal distribution that suggests a link between ependymomagenesis and alterations of the biological processes involved in embryonic brain development. In children, EPN most often arises intra-cranially and is associated with an adverse outcome. Emerging evidence shows that EPN displays large intra-patient heterogeneity. In this review, after touching on EPN inter-tumoral heterogeneity, we focus on the sources of ITH in pediatric intra-cranial EPN in the framework of the CSC paradigm. We also examine how single-cell technology has shed new light on the complexity and developmental origins of EPN and the potential impact that this understanding may have on the therapeutic strategies against this deadly pediatric malignancy.

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Infratentorial C11orf95-fused gliomas share histologic, immunophenotypic, and molecular characteristics of supratentorial RELA-fused ependymoma

Cited by 16 publications

References 8 publications

Ependymoma‐like tumor with mesenchymal differentiation harboring C11orf95‐NCOA1/2 or ‐RELA fusion: A hitherto unclassified tumor related to ependymoma

Ependymoma‐like tumor with mesenchymal differentiation harboring C11orf95‐NCOA1/2 or ‐RELA fusion: A hitherto unclassified tumor related to ependymoma

Molecular Stratification of Childhood Ependymomas as a Basis for Personalized Diagnostics and Treatment

Cell-of-Origin and Genetic, Epigenetic, and Microenvironmental Factors Contribute to the Intra-Tumoral Heterogeneity of Pediatric Intracranial Ependymoma

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